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Journal articles on the topic 'Imidazoline-2 receptors'

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Published: 9 March 2023

Last updated: 10 March 2023

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1

Golubenkova, Alexandra S., Nikita E. Golantsov, Alexey A. Festa, and Leonid G. Voskressensky. "1-Benzyl-2-(thien-2-yl)-4,5-dihydro-1H-imidazole." Molbank 2020, no. 2 (May 18, 2020): M1137. http://dx.doi.org/10.3390/m1137.

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Imidazolines are a valuable class of organic compounds, namely ligands of imidazoline receptors, chiral ligands for metal catalysis, synthetic intermediates. The title compound has been prepared through a modified procedure, employing N-benzylethylenediamine and thiophene-2-carbaldehyde under the action of N-bromosuccinimide (NBS) in dichloromethane (DCM) in a good 78% yield.

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2

Li, Jun-Xu. "Imidazoline I 2 receptors: An update." Pharmacology & Therapeutics 178 (October 2017): 48–56. http://dx.doi.org/10.1016/j.pharmthera.2017.03.009.

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Bagán, Andrea, Sònia Abás, Sergio Rodríguez-Arévalo, Gemma Rodríguez-Arévalo, Fotini Vasilopoulou, Christian Griñán-Ferré, Mercè Pallàs, et al. "(2-Imidazolin-4-yl)phosphonates: Green Chemistry and Biology Walk Together." Proceedings 22, no. 1 (September 10, 2019): 97. http://dx.doi.org/10.3390/proceedings2019022097.

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4

Takamatsu, Isao, Ayano Iwase, Makoto Ozaki, Tomiei Kazama, Keiji Wada, and Masayuki Sekiguchi. "Dexmedetomidine Reduces Long-term Potentiation in Mouse Hippocampus." Anesthesiology 108, no. 1 (January 1, 2008): 94–102. http://dx.doi.org/10.1097/01.anes.0000296076.04510.e1.

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Background Dexmedetomidine (Precedex; Abbott Laboratories, Abbott Park, IL) is a selective alpha2-adrenergic agonist that also has affinity for imidazoline receptors. In clinical studies, dexmedetomidine has sedative effects and impairs memory, but the action of dexmedetomidine on synaptic plasticity in the brain has yet to be established. In the present study, the authors investigated the effects of dexmedetomidine on two forms of synaptic plasticity-long-term potentiation (LTP) and paired-pulse facilitation-in the CA1 region of mouse hippocampal slices. Methods The authors recorded Schaffer collateral-evoked field excitatory postsynaptic potentials from mouse hippocampal slices in CA1 stratum radiatum. The slope of the rising phase of the field excitatory postsynaptic potential was used to estimate the strength of synaptic transmission. Results Application of dexmedetomidine for 20 min before "theta burst" stimulation dose-dependently attenuated LTP, and half-inhibitory concentration of dexmedetomidine was 28.6 +/- 5.7 nm. The inhibitory effect of dexmedetomidine on LTP was not abolished by an alpha2-adrenoceptor antagonist (yohimbine), an imidazoline type 1 receptor and alpha2-adrenoceptor antagonist (efaroxan), an alpha1-adrenoceptor antagonist (prazosin), or a gamma-aminobutyric acid type A receptor antagonist (picrotoxin). However, an imidazoline type 2 receptor and alpha2-adrenoceptor antagonist (idazoxan) completely blocked the dexmedetomidine-induced attenuation. Furthermore, 2-benzofuranyl-2-imidaloline, a selective imidazoline type 2 receptor ligand, reduced LTP. 2-(4,5-dihydroimidaz-2-yl)-quinoline, another imidazoline type 2 receptor ligand, abolished the 2-benzofuranyl-2-imidaloline-induced attenuation, but the inhibitory effect of dexmedetomidine on LTP was not abolished by 2-(4,5-dihydroimidaz-2-yl)-quinoline. Dexmedetomidine did not affect paired-pulse facilitation. Conclusion Dexmedetomidine impairs LTP in area CA1 of the mouse hippocampus via imidazoline type 2 receptors and alpha2-adrenoceptors.

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Soldatov, Vladislav O., Elena A. Shmykova, Marina A. Pershina, Andrey O. Ksenofontov, Yaroslav M. Zamitsky, Alexandr L. Kulikov, Anna A. Peresypkina, Anton P. Dovgan, and Yuliya V. Belousova. "Imidazoline receptors agonists: possible mechanisms of endothelioprotection." Research Results in Pharmacology 4, no. 2 (July 19, 2018): 11–19. http://dx.doi.org/10.3897/rrpharmacology.4.27221.

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Imidazoline receptor agonists are one of the groups of contemporary antihypertensive drugs with the pleiotropic cardiovascular effects. In this review, the historical, physiological, pathophysiological aspects concerning imidazoline receptor agonists and possible mechanisms for their participation in endothelioprotection were considered. Illuminated the molecular biology of each subtype of imidazoline receptors and their significance in the pharmacological correction of cardiovascular disease. IR type 1 are localized in the brain nucleus, carrying out the descending tonic control of sympathetic activation, as well as in the endothelial cells of the vessels and kidneys. Their activation leads to a decrease in blood pressure, slowing the remodeling of the vascular wall and increasing sodium nares. IR type 2 is expressed predominantly in the adrenal gland, fat and muscle tissues. The physiological effects of their stimulation are associated with an increase in glucose utilization by peripheral tissues. IR type 3 are mainly present in pancreatic cells and are associated with the regulation of insulin secretion. Their stimulation leads to an increase in insulin liberation. Thus, IR agonists are able to improve endothelial function through various mechanisms, including blood pressure reduction, improvement in metabolic profile, and direct positive effects on the vascular wall. Current information on the pharmacological effects of this group compounds allows us to conclude that they are a promising group for correcting endothelial dysfunction and complications associated with it.

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BOUSQUET, P. "Central I1- imidazoline receptors and blood pressure: a crosstalk with ?2-adrenergic receptors." American Journal of Hypertension 17, no. 5 (May 2004): S13. http://dx.doi.org/10.1016/j.amjhyper.2004.03.026.

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7

Lione, Lisa A., David J. Nutt, and Alan L. Hudson. "Characterisation and localisation of []2-(2-benzofuranyl)-2-imidazoline binding in rat brain: a selective ligand for imidazoline I2 receptors." European Journal of Pharmacology 353, no. 1 (July 1998): 123–35. http://dx.doi.org/10.1016/s0014-2999(98)00389-6.

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8

Callado, Luis F., Ana I. Maeztu, Javier Ballesteros, Miguel Gutiérrez, and J. Javier Meana. "Differential [3H]idazoxan and [3H]2-(2-benzofuranyl)-2-imidazoline (2-BFI) binding to imidazoline I2 receptors in human postmortem frontal cortex." European Journal of Pharmacology 423, no. 2-3 (July 2001): 109–14. http://dx.doi.org/10.1016/s0014-2999(01)01097-4.

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Lione, Lisa A., David J. Nutt, and Alan L. Hudson. "[3H]2-(2-Benzofuranyl)-2-imidazoline: a new selective high affinity radioligand for the study of rabbit brain imidazoline I2 receptors." European Journal of Pharmacology 304, no. 1-3 (May 1996): 221–29. http://dx.doi.org/10.1016/0014-2999(96)00131-8.

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10

Bousquet, P., G. Bricca, M. Dontenwill, J. Feldman, H. Greney, A. Belcourt, J. Stutzmann, and E. Tibiriça. "L 2 - FROM THE α2-ADRENOCEPTORS TO THE IMIDAZOLINE PREFERRING RECEPTORS." Fundamental & Clinical Pharmacology 6, S1 (December 1992): 15s—21s. http://dx.doi.org/10.1111/j.1472-8206.1992.tb00137.x.

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11

HIEBLE, J. PAUL, and ROBERT R. RUFFOLO. "Possible Structural and Functional Relationships between Imidazoline Receptors and ?2-Adrenoceptors." Annals of the New York Academy of Sciences 763, no. 1 The Imidazoli (July 1995): 8–21. http://dx.doi.org/10.1111/j.1749-6632.1995.tb32387.x.

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12

Alemany, R., Gabriel Olmos, and Jesús A. García-Sevilla. "Labelling of I2B-imidazoline receptors by [3H]2-(2-benzofuranyl)-2-imidazoline (2-BFI) in rat brain and liver: characterization, regulation and relation to monoamine oxidase enzymes." Naunyn-Schmiedeberg's Archives of Pharmacology 356, no. 1 (June 16, 1997): 39–47. http://dx.doi.org/10.1007/pl00005026.

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13

Boxwalla, Mustufa, George Matwyshyn, Bhagya L. Puppala, Shridhar V. Andurkar, and Anil Gulati. "Involvement of imidazoline and opioid receptors in the enhancement of clonidine-induced analgesia by sulfisoxazole." Canadian Journal of Physiology and Pharmacology 88, no. 5 (May 2010): 541–52. http://dx.doi.org/10.1139/y10-007.

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Clonidine, an α2-adrenergic agonist, has been demonstrated to produce significant analgesia and potentiate morphine analgesia. Endothelin (ETA) receptor antagonists have also been found to potentiate the antinociceptive response to morphine. Clonidine and ET have been reported to have cardiovascular interactions involving the sympathetic nervous system, but it is not known whether ETA receptor antagonist affects clonidine analgesia. This study examined the influence of sulfisoxazole (ETA receptor antagonist) on clonidine analgesia. Male Swiss Webster mice were used to determine antinociceptive response of drugs by measuring tail-flick latency. The effect of clonidine (0.3, 1.0, and 3.0 mg/kg, i.p.) alone or in combination with sulfisoxazole (25, 75, and 225 mg/kg, p.o.) on analgesia and body temperature was determined. Clonidine produced a dose-dependent analgesia and hypothermia. Sulfisoxazole (25, 75, and 225 mg/kg), when administered with clonidine (0.3 mg/kg), significantly potentiated (31% increase in area under the curve (AUC)) the analgesic effect of clonidine. Yohimbine (α2-adrenergic receptor antagonist) did not affect analgesic effect of clonidine plus sulfisoxazole. Idazoxan (I1-imidazoline and α2-adrenergic receptor antagonist) reduced (47% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. Treatment with naloxone reduced (46% decrease in AUC) the analgesic effect of clonidine plus sulfisoxazole. The effect of another ETA receptor antagonist, BMS-182874 (2, 10, and 50 µg, i.c.v.) was studied, and it was found that the dose of 10 µg significantly potentiated (26% increase in AUC) the analgesic effect of clonidine. These results indicate that sulfisoxazole, an ETA receptor antagonist, potentiates the analgesic effect of clonidine, which could be mediated through I1-imidazoline receptors and opioid receptors.

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14

Glennon, Richard A., Brian Grella, Robin J. Tyacke, Alice Lau, Julie Westaway, and Alan L. Hudson. "Binding of β-carbolines at imidazoline I 2 receptors: a structure–affinity investigation." Bioorganic & Medicinal Chemistry Letters 14, no. 4 (February 2004): 999–1002. http://dx.doi.org/10.1016/j.bmcl.2003.11.078.

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15

Dahmani, Souhayl, Andrea Paris, Virginie Jannier, Lutz Hein, Danielle Rouelle, Jens Scholz, Pierre Gressens, and Jean Mantz. "Dexmedetomidine Increases Hippocampal Phosphorylated Extracellular Signal–regulated Protein Kinase 1 and 2 Content by an α2-Adrenoceptor–independent Mechanism." Anesthesiology 108, no. 3 (March 1, 2008): 457–66. http://dx.doi.org/10.1097/aln.0b013e318164ca81.

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Background Dexmedetomidine is a potent and selective alpha2-adrenoceptor (alpha2AR) agonist that exhibits a broad pattern of actions, including sedation, analgesia, and neuroprotection. Recent studies have emphasized the role of phosphorylated extracellular signal-regulated protein kinases (pERK1 and 2) in coupling rapid events such as neurotransmitter release and receptor stimulation long-lasting changes in synaptic plasticity and cell survival. Here, the authors hypothesized that dexmedetomidine increases pERK1 and 2 content and examined the mechanisms involved in this effect. Methods The effects of dexmedetomidine and their sensitivity to various pharmacologic agents on expression of pERK1 and 2 were studied by Western blots in hippocampal slices obtained from rats, wild-type mice, and mice carrying targeted deletions of the alpha2AR subtypes. Results Dexmedetomidine induced a concentration-related increase in the expression of pERK1 and 2 in rat hippocampal slices (EC50 [95% confidence interval] for pERK1, 0.97 [0.68-1.37] microm; for pERK2, 1.15 [0.62-2.14] microm). This effect was insensitive to the inhibitors of the alpha2AR-mediated signaling pathway, to prazosin, and to PP2, an inhibitor of the focal adhesion kinase-Src kinases. In contrast, it was still present in mice deleted for each of the alpha2AR subtypes and was markedly decreased by the antagonist of the I1-imidazoline receptors efaroxan, by phospholipase C and protein kinase C inhibitors, and by PD 098059, a direct inhibitor of ERK1 and 2 phosphorylation. Conclusion Dexmedetomidine increases the expression of pERK1 and 2 via mechanisms independent of alpha2AR activation. The I1-imidazoline receptors likely contribute to these effects. The results may be relevant to some long-term effects (e.g., neuroprotective) of dexmedetomidine in the brain.

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Giorgioni, Gianfabio, Dario Ambrosini, Cristian Vesprini, Alan Hudson, Cinzia Nasuti, Antonio Di Stefano, Piera Sozio, et al. "Novel imidazoline compounds as partial or full agonists of D2-like dopamine receptors inspired by I2-imidazoline binding sites ligand 2-BFI." Bioorganic & Medicinal Chemistry 18, no. 19 (October 2010): 7085–91. http://dx.doi.org/10.1016/j.bmc.2010.08.005.

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SCHAFER, U. "Moxonidine Displays a Presynaptic Alpha-2-Adrenoceptor-Dependent Synergistic Sympathoinhibitory Action at Imidazoline-1 Receptors." Annals of the New York Academy of Sciences 1009, no. 1 (December 1, 2003): 265–69. http://dx.doi.org/10.1196/annals.1304.033.

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18

Chang, Chin-Hong, Pin-Chun Chao, Ho-Shan Niu, Gin-Chi Huang, Li-Jen Chen, and Juei-Tang Cheng. "Canavanine activates imidazoline I-2 receptors to reduce hyperglycemia in type 1-like diabetic rats." Chemico-Biological Interactions 240 (October 2015): 304–9. http://dx.doi.org/10.1016/j.cbi.2015.08.019.

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19

Fuder, Hermann, and Petra Schwarz. "Desensitization of inhibitory prejunctional ?2-adrenoceptors and putative imidazoline receptors on rabbit heart sympathetic nerves." Naunyn-Schmiedeberg's Archives of Pharmacology 348, no. 2 (August 1993): 127–33. http://dx.doi.org/10.1007/bf00164788.

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20

Allen, A. M., and P. G. Guyenet. "Alpha 2-adrenoceptor-mediated inhibition of bulbospinal barosensitive cells of rat rostral medulla." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 265, no. 5 (November 1, 1993): R1065—R1075. http://dx.doi.org/10.1152/ajpregu.1993.265.5.r1065.

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Bulbospinal barosensitive neurons of the rostral ventrolateral medulla (RVLM cells; presumed sympathetic vasomotor premotor neurons) were recorded with iontophoretic electrodes in urethan-anesthetized rats. The majority of these cells were insensitive to intravenous clonidine (Clo; up to 20 micrograms/kg) and insensitive to iontophoretically applied Clo or alpha-methylnorepinephrine (alpha-MNE). These cells (n = 47 of 76) had a spinal conduction velocity of 4.1 +/- 0.2 m/s and a mean firing rate of 20 +/- 1 spikes/s. A second population (n = 29) was powerfully inhibited by intravenous Clo (5-10 micrograms/kg, activity decreased by 83 +/- 11%), iontophoretically applied Clo (decreased by 51 +/- 7%), and iontophoresis of alpha-MNE (decreased by 69 +/- 3%). These cells had a slower conduction velocity (2.0 +/- 0.3 m/s) and a much slower discharge rate (6 +/- 1 spikes/s). Both populations were pulse synchronous at resting arterial pressure. The inhibitory effects produced by iontophoresis of alpha-MNE or Clo were reduced to the same degree (86-98%) by iontophoresis of idazoxan (an alpha 2-adrenergic antagonist with imidazoline structure) and by iontophoresis of piperoxan (65-77%, a nonimidazoline alpha 2-antagonist). The inhibition of RVLM cells by intravenous Clo was reversed by iontophoresis of idazoxan and by intravenous injection of yohimbine (nonimidazoline alpha 2-antagonists). These data suggest that 1) intravenous Clo only inhibits a subpopulation of RVLM sympathetic premotoneurons, possibly the C1 adrenergic cells, 2) this effect of Clo is due to activation of alpha 2-adrenergic receptors rather than nonadrenergic imidazoline binding sites, and 3) these alpha 2-receptors are located on or close to the Clo-sensitive cells and may be continuously activated by endogenously released catecholamines.

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DeBernardis, John F., John J. Kyncl, Fatima Z. Basha, David L. Arendsen, Yvonne C. Martin, Martin Winn, and Daniel J. Kerkman. "Conformationally defined adrenergic agents. 2. Catechol imidazoline derivatives: biological effects at .alpha.1 and .alpha.2 adrenergic receptors." Journal of Medicinal Chemistry 29, no. 4 (April 1986): 463–67. http://dx.doi.org/10.1021/jm00154a006.

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REGUNATHAN, SOUNDARARAJAN, SONJA BRAMWELL, and DONALD J. REIS. "Effects of Rilmenidine on Signal Transduction Mechanisms Associated with ?2-Adrenergic and Imidazoline Receptors in Brain." Annals of the New York Academy of Sciences 763, no. 1 The Imidazoli (July 1995): 290–94. http://dx.doi.org/10.1111/j.1749-6632.1995.tb32415.x.

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Bach, K. B., and G. S. Mitchell. "Hypercapnia-induced long-term depression of respiratory activity requires α2-adrenergic receptors." Journal of Applied Physiology 84, no. 6 (June 1, 1998): 2099–105. http://dx.doi.org/10.1152/jappl.1998.84.6.2099.

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We investigated the effects of repeated hypercapnic episodes (inspired CO2fraction = 0.10) on posthypercapnic respiratory nerve discharge. Anesthetized (urethan), vagotomized, and artificially ventilated rats were presented with three consecutive 5-min episodes of hyperoxic hypercapnia, separated by 5 min of hyperoxic normocapnia (inspired O2 fraction = 0.5). Respiratory nerve discharge and blood gases were recorded before and 30 and 60 min after the final hypercapnic episode. Posthypercapnia, arterial[Formula: see text] was maintained within 1 Torr of initial baseline values. Integrated phrenic and hypoglossal burst amplitudes decreased posthypercapnia by up to 46 ± 17 and 55 ± 13% of baseline values, respectively, and remained reduced for at least 1 h [long-term depression (LTD)]. The protocol was repeated in rats pretreated with the α2-adrenergic antagonists yohimbine HCl (0.5 mg/kg; n = 7) or 2-[2-(2-methoxy-1,4-benzodioanyl)]imidazoline (RX-821002) HCl (0.25 mg/kg; n = 3). Both drugs attenuated LTD in the phrenic and hypoglossal neurograms. Results indicate that episodic hypercapnia elicits a yohimbine- and RX-821002-sensitive LTD of respiratory nerve activity in rats, suggesting that LTD requires α2-receptor activation.

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Lee, J. P., W. Chen, H. T. Wu, K. C. Lin, and J. T. Cheng. "Metformin can Activate Imidazoline I-2 Receptors to Lower Plasma Glucose in Type 1-like Diabetic Rats." Hormone and Metabolic Research 43, no. 01 (October 13, 2010): 26–30. http://dx.doi.org/10.1055/s-0030-1267169.

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Szabo, Bela, and Rolf Urban. "Role of alpha-2 and imidazoline receptors in the central sympathoinhibition caused by guanabenz, rilmenidine and moxonidine." Pharmacological Research 31 (January 1995): 329. http://dx.doi.org/10.1016/1043-6618(95)87575-1.

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Codd, E. "Alpha2-adrenoceptors vs. imidazoline receptors: implications for Î±2-mediated analgesia and other non-cardiovascular therapeutic uses." Life Sciences 56, no. 2 (1995): 63–74. http://dx.doi.org/10.1016/0024-3205(94)00415-o.

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Ferreira, Renan B., Mariana G. de Oliveira, Edson Antunes, Wanda P. Almeida, Badr M. Ibrahim, and Abdel A. Abdel-Rahman. "New 2-Aminothiazoline derivatives lower blood pressure of spontaneously hypertensive rats (SHR) via I1-imidazoline and alpha-2 adrenergic receptors activation." European Journal of Pharmacology 791 (November 2016): 803–10. http://dx.doi.org/10.1016/j.ejphar.2016.10.009.

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Contino, Marialessandra, Antonio Carrieri, Francesco Berardi, Marcello Leopoldo, Roberto Perrone, Russell Thomas, and Nicola Antonio Colabufo. "Guinea-pig ileum as ex vivo model useful to characterize ligands displaying Imidazoline I2 and Adrenergic alpha2 mixed activity: a preliminary study." Drugs and Therapy Studies 3, no. 1 (January 22, 2013): 1. http://dx.doi.org/10.4081/dts.2013.e1.

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The lack of an effective analgesic treatment makes pain a clinical challenge and the need of a novel approach to identify new agents is urgent. In this scenario I2-ligands can be considered an alternative strategy in pain therapy. The development of an <em>ex vivo</em> model useful for the evaluation of functional activities at both a2 and I2-IBs (imidazoline binding sites) is an important task in pharmacological sciences since several I2 ligands display activity also towards a receptors. The present study aims to develop an <em>ex vivo</em> model for estimating the activity of I2-IBs ligands in a biological sample where a1 and a2 adrenergic receptors are present. For this purpose the imidalzoline endogenous ligand, harmane, reference compounds, 2BFI and BU224, and imidazoline derivatives 1-3 have been selected taking into account their in vitro activity towards IBs and adrenergic receptors. All compounds have been tested <em>ex vivo</em> in guinea pig-ileum where a2A-ARs are prejunctionally and I2-IBS postjunctionally localized. Adrenergic component has been identified by the studying the interference of compounds on the electrically-evoked contraction while I2-IBs activity by testing the ability of compounds to inhibit the carbachol-evoked contractions in the presence of prazosin to mask the a1 adrenoceptors. Compounds 1 and 2 were found I2-IBs antago nists (pIC50=4.2 and 4.0, respectively) whereas compound 3 was I2-IBs agonist (EC50=0.38 mM); All ligands were a2 adrenergic agonists. This paper suggests guinea-pig ileum as the first <em>ex vivo</em> approach for establishing both the intrinsic activity of I2-IBs ligands and the physiological correlation between IBs and adrenergic system.

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BRUBAN, V. "Central blood pressure effects of S 23515, a ligand highly selective for imidazoline receptors over $alpha;2-adrenoceptors." American Journal of Hypertension 12, no. 4 (April 1999): 107. http://dx.doi.org/10.1016/s0895-7061(99)80369-0.

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Su, Chin-Hui, I. Min Liu, Hsien-Hui Chung, and Juei-Tang Cheng. "Activation of I2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats." Neuroscience Letters 457, no. 3 (July 2009): 125–28. http://dx.doi.org/10.1016/j.neulet.2009.03.093.

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Wang, Wei-Zhong, Li-Gang Wang, Lie Gao, and Wei Wang. "Contribution of AMPA/kainate receptors in the rostral ventrolateral medulla to the hypotensive and sympathoinhibitory effects of clonidine." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 293, no. 3 (September 2007): R1232—R1238. http://dx.doi.org/10.1152/ajpregu.00233.2007.

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The depressor and sympathoinhibitory effect of the imidazoline drug clonidine is reported to be associated with functional states of the central glutamate receptors. The rostral ventrolateral medulla (RVLM) has been recognized as a specific target area for mediating the central depressor mechanism of clonidine. The objective of this study was to determine the role of the glutamate receptor subtype α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor within the RVLM in clonidine-induced depressor and sympathoinhibitory action in anesthetized normotensive rats. Unilateral microinjection of 200 pmol of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a potent AMPA/kainate receptor antagonist, into the RVLM completely abolished the pressor action evoked by AMPA (5 pmol) without affecting the pressor action of N-methyl-d-aspartate (20 pmol). Pretreatment with intra-RVLM injection of CNQX (20 and 200 pmol) dose dependently attenuated the reduction in blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) elicited by intra-RVLM clonidine (5 nmol) or intravenous clonidine (10 μg/kg), while 2 pmol of CNQX did not alter clonidine-induced cardiovascular action. Furthermore, the decreases in BP, HR, and RSNA evoked by intravenous clonidine (10 μg/kg) or intra-RVLM clonidine (5 nmol) were reversed when CNQX (20 and 200 pmol) was subsequently injected into the RVLM. In conclusion, these data show that blockade of AMPA/kainate receptors in the RVLM significantly antagonizes decreases in BP, HR, and sympathetic activity induced by clonidine, suggesting that the AMPA/kainate receptors within the RVLM contribute to the depressor and sympathoinhibitory effect of clonidine.

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Sanderson, Lisa, Marcelo da Silva, Gayathri N. Sekhar, Rachel C. Brown, Hollie Burrell-Saward, Mehmet Fidanboylu, Bo Liu, et al. "Drug reformulation for a neglected disease. The NANOHAT project to develop a safer more effective sleeping sickness drug." PLOS Neglected Tropical Diseases 15, no. 4 (April 15, 2021): e0009276. http://dx.doi.org/10.1371/journal.pntd.0009276.

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Background Human African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. The objective of our research programme was to develop an intravenous formulation of pentamidine which increases CNS exposure by some 10–100 fold, leading to efficacy against a model of stage 2 HAT. This target candidate profile is in line with drugs for neglected diseases inititative recommendations. Methodology To do this, we evaluated the physicochemical and structural characteristics of formulations of pentamidine with Pluronic micelles (triblock-copolymers of polyethylene-oxide and polypropylene oxide), selected candidates for efficacy and toxicity evaluation in vitro, quantified pentamidine CNS delivery of a sub-set of formulations in vitro and in vivo, and progressed one pentamidine-Pluronic formulation for further evaluation using an in vivo single dose brain penetration study. Principal Findings Screening pentamidine against 40 CNS targets did not reveal any major neurotoxicity concerns, however, pentamidine had a high affinity for the imidazoline2 receptor. The reduction in insulin secretion in MIN6 β-cells by pentamidine may be secondary to pentamidine-mediated activation of β-cell imidazoline receptors and impairment of cell viability. Pluronic F68 (0.01%w/v)-pentamidine formulation had a similar inhibitory effect on insulin secretion as pentamidine alone and an additive trypanocidal effect in vitro. However, all Pluronics tested (P85, P105 and F68) did not significantly enhance brain exposure of pentamidine. Significance These results are relevant to further developing block-copolymers as nanocarriers, improving BBB drug penetration and understanding the side effects of pentamidine.

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Narayanaswami, Vidya, Kenneth Dahl, Vadim Bernard-Gauthier, Lee Josephson, Paul Cumming, and Neil Vasdev. "Emerging PET Radiotracers and Targets for Imaging of Neuroinflammation in Neurodegenerative Diseases: Outlook Beyond TSPO." Molecular Imaging 17 (January 1, 2018): 153601211879231. http://dx.doi.org/10.1177/1536012118792317.

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The dynamic and multicellular processes of neuroinflammation are mediated by the nonneuronal cells of the central nervous system, which include astrocytes and the brain’s resident macrophages, microglia. Although initiation of an inflammatory response may be beneficial in response to injury of the nervous system, chronic or maladaptive neuroinflammation can have harmful outcomes in many neurological diseases. An acute neuroinflammatory response is protective when activated neuroglia facilitate tissue repair by releasing anti-inflammatory cytokines and neurotrophic factors. On the other hand, chronic neuroglial activation is a major pathological mechanism in neurodegenerative diseases, likely contributing to neuronal dysfunction, injury, and disease progression. Therefore, the development of specific and sensitive probes for positron emission tomography (PET) studies of neuroinflammation is attracting immense scientific and clinical interest. An early phase of this research emphasized PET studies of the prototypical imaging biomarker of glial activation, translocator protein-18 kDa (TSPO), which presents difficulties for quantitation and lacks absolute cellular specificity. Many alternate molecular targets present themselves for PET imaging of neuroinflammation in vivo, including enzymes, intracellular signaling molecules as well as ionotropic, G-protein coupled, and immunoglobulin receptors. We now review the lead structures in radiotracer development for PET studies of neuroinflammation targets for neurodegenerative diseases extending beyond TSPO, including glycogen synthase kinase 3, monoamine oxidase-B, reactive oxygen species, imidazoline-2 binding sites, cyclooxygenase, the phospholipase A2/arachidonic acid pathway, sphingosine-1-phosphate receptor-1, cannabinoid-2 receptor, the chemokine receptor CX3CR1, purinergic receptors: P2X7 and P2Y12, the receptor for advanced glycation end products, Mer tyrosine kinase, and triggering receptor expressed on myeloid cells-1. We provide a brief overview of the cellular expression and function of these targets, noting their selectivity for astrocytes and/or microglia, and highlight the classes of PET radiotracers that have been investigated in early-stage preclinical or clinical research studies of neuroinflammation.

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Inagaki, Manami, Masayuki Somei, Tatsunori Oguchi, Ran Ono, Sachie Fukutaka, Ikumi Matsuoka, Mayumi Tsuji, and Katsuji Oguchi. "Neuroprotective Effects of Dexmedetomidine against Thapsigargin-induced ER-stress via Activity of α₂-adrenoceptors and Imidazoline Receptors." AIMS Neuroscience 3, no. 2 (2016): 237–52. http://dx.doi.org/10.3934/neuroscience.2016.2.237.

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Kozaeva, L. P., N. V. Korobov, and O. S. Medvedev. "Effect of Moxonidine on Contractile Activity of Isolated Large Intestine in Mice: Role of 2-Adrenoceptors and Ii-Imidazoline Receptors." Bulletin of Experimental Biology and Medicine 137, no. 3 (March 2004): 252–54. http://dx.doi.org/10.1023/b:bebm.0000031562.09615.06.

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Lin, K. C., L. R. Yeh, L. J. Chen, Y. J. Wen, K. C. Cheng, and J. T. Cheng. "Plasma Glucose-lowering Action of Allantoin is Induced by Activation of Imidazoline I-2 Receptors in Streptozotocin-induced Diabetic Rats." Hormone and Metabolic Research 44, no. 01 (December 6, 2011): 41–46. http://dx.doi.org/10.1055/s-0031-1295439.

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Maltsev, Alexander V., Yuri M. Kokoz, Edward V. Evdokimovskii, Oleg Y. Pimenov, Santiago Reyes, and Alexey E. Alekseev. "Alpha-2 adrenoceptors and imidazoline receptors in cardiomyocytes mediate counterbalancing effect of agmatine on NO synthesis and intracellular calcium handling." Journal of Molecular and Cellular Cardiology 68 (March 2014): 66–74. http://dx.doi.org/10.1016/j.yjmcc.2013.12.030.

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Kagawa, K., T. Mammoto, T. Kamibayashi, K. Takada, Y. Hayashi, and I. Yoshiya. "A661 Activation of alpha sub 2 adrenoceptors but not Imidazoline receptors attenuate the hemodynamic response against noxious stimuli in rats." Anesthesiology 87, Supplement (September 1997): 661A. http://dx.doi.org/10.1097/00000542-199709001-00661.

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Yang, T. T., P. M. Ku, C. T. Hsu, H. H. Chung, W. J. Lee, and J. T. Cheng. "Mediation of AMP Kinase in the Increase of Glucose Uptake in L6 Cells Induced by Activation of Imidazoline I-2 Receptors." Hormone and Metabolic Research 45, no. 05 (December 7, 2012): 359–63. http://dx.doi.org/10.1055/s-0032-1331184.

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Orer, H. S., S. Zhong, S. M. Barman, and G. L. Gebber. "Central catecholaminergic neurons are involved in expression of the 10-Hz rhythm in SND." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 270, no. 2 (February 1, 1996): R333—R341. http://dx.doi.org/10.1152/ajpregu.1996.270.2.r333.

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We studied the effects of adrenoceptor agonists and antagonists on sympathetic nerve discharge (SND) of urethan-anesthetized, baroreceptor-denervated cats. In cats in which a 10-Hz rhythm coexisted with irregular 2- to 6-Hz oscillations in SND, intravenous clonidine, an alpha 2-adrenoceptor agonist, blocked the 10-Hz rhythm without affecting power at lower frequencies. In contrast, power at frequencies < or = 6 Hz was depressed by clonidine in cats in which the 10-Hz rhythm was absent. These effects were reversed by intravenous administration of alpha 2-adrenoceptor antagonists, idazoxan and rauwolscine. Rauwolscine is devoid of affinity for imidazoline receptors. Furthermore, in cats untreated with clonidine, idazoxan and rauwolscine enhanced or induced the 10-Hz rhythm without affecting power at lower frequencies. Prazosin, an alpha 1-adrenoceptor antagonist, selectively blocked the 10-Hz rhythm in SND. Finally, the 10-Hz rhythm in SND was blocked by microinjection of clonidine into the rostral or caudal ventrolateral medulla. The results support the view that central catecholaminergic neurons play a role in expression of the 10-Hz rhythm in SND.

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Kawamura, Kazunori, Mika Naganawa, Fujiko Konno, Joji Yui, Hidekatsu Wakizaka, Tomoteru Yamasaki, Kazuhiko Yanamoto, et al. "Imaging of I2-imidazoline receptors by small-animal PET using 2-(3-fluoro-[4-11C]tolyl)-4,5-dihydro-1H-imidazole ([11C]FTIMD)." Nuclear Medicine and Biology 37, no. 5 (July 2010): 625–35. http://dx.doi.org/10.1016/j.nucmedbio.2010.02.013.

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Duflo, Frédéric, Dawn Conklin, Xinhui Li, and James C. Eisenach. "Spinal Adrenergic and Cholinergic Receptor Interactions Activated by Clonidine in Postincisional Pain." Anesthesiology 98, no. 5 (May 1, 2003): 1237–42. http://dx.doi.org/10.1097/00000542-200305000-00028.

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Background Previous pharmacologic and molecular studies suggest that the alpha(2)-adrenoceptor subtype A is the target for spinally administered alpha(2)-adrenergic agonists, i.e., clonidine, for pain relief. However, intrathecally administered alpha(2) C antisense oligodeoxynucleotide was recently reported to decrease antinociception induced by clonidine in the rat, suggesting non-A sites may be important as well. The current study sought to determine the subtype of alpha(2) adrenoceptors activated by clonidine in a rodent model for human postoperative pain, and to examine its interaction with spinal cholinergic receptors. Methods Postoperative hypersensitivity was produced in rats by plantar incision of the hind paw and punctuate mechanical stimuli were applied around the wound 24 h after surgery. Effects of intrathecal clonidine and 2-(2,6-diethylphenylamino)-2-imidazoline (ST91) on withdrawal thresholds to the stimulus were determined. To examine the adrenoceptor subtype and its interaction with spinal cholinergic receptors, animals were intrathecally pretreated with vehicles BRL44408 (an alpha(2) A subtype-preferring antagonist), ARC239 (an alpha(2) non-A subtype-preferring antagonist), atropine (a muscarinic antagonist), and mecamylamine (a nicotinic antagonist). Results Intrathecal ST91 showed a significantly greater efficacy when compared with clonidine. The analgesic effect of clonidine was diminished by pretreatment with either adrenoceptor antagonist, whereas the effect of ST91 was solely blocked by ARC239 pretreatment. Atropine and mecamylamine abolished the effect of clonidine effect but not the effect of ST91. Conclusions Both alpha(2) A and alpha(2) non-A adrenoceptors, as well as spinal cholinergic activation, are important to the antihypersensitivity effect of clonidine after surgery. ST91 is more efficacious in this model than clonidine and relies entirely on alpha(2) non-A adrenoceptors.

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Stone, Laura S., Kelley F. Kitto, James C. Eisenach, Carolyn A. Fairbanks, and George L. Wilcox. "ST91 [2-(2,6-Diethylphenylamino)-2-imidazoline Hydrochloride]-Mediated Spinal Antinociception and Synergy with Opioids Persists in the Absence of Functional α-2A- or α-2C-Adrenergic Receptors." Journal of Pharmacology and Experimental Therapeutics 323, no. 3 (September 13, 2007): 899–906. http://dx.doi.org/10.1124/jpet.107.125526.

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Lui, Tai-Ngar, Chiung-Wen Tsao, Shih-Yun Huang, Chin-Hong Chang, and Juei-Tang Cheng. "Activation of imidazoline I 2B receptors is linked with AMP kinase pathway to increase glucose uptake in cultured C 2 C 12 cells." Neuroscience Letters 474, no. 3 (May 2010): 144–47. http://dx.doi.org/10.1016/j.neulet.2010.03.024.

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FLAMEZ, A., M. GILLARD, J. P. DE BACKER, G. VAUQUELIN, and M. NOYER. "THE NOVEL ALPHA 2 -ADRENOCEPTOR AGONIST [ 3 H]MIVAZEROL BINDS TO NON-ADRENERGIC BINDING SITES IN HUMAN STRIATUM MEMBRANES THAT ARE DISTINCT FROM IMIDAZOLINE RECEPTORS." Neurochemistry International 31, no. 1 (July 1997): 125–29. http://dx.doi.org/10.1016/s0197-0186(96)00117-9.

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Ivanov, Valerii S., Aleksei B. Seleznev, Evgenii V. Raguzin, Evgenii V. Ivchenko, Tatyana B. Pechurina, Igor M. Ivanov, Daniil D. Glushenko, and Ruslan V. Glushakov. "Assessment of naphazoline effect on erythrocyte superoxide dismutase activity in rats under experimental modeling of acute radiation sickness." Science and Innovations in Medicine 8, no. 1 (February 11, 2023): 60–65. http://dx.doi.org/10.35693/2500-1388-2023-8-1-60-65.

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Aim to assess the activity of superoxide dismutase in erythrocytes of rats after a single intramuscular injection of naphazoline in radiofrequency dose and in experimental simulation of acute radiation sickness. Material and methods. The activity of erythrocytes superoxide dismutase (SOD) after single intramuscular injection of nafazoline in experimental modeling of acute radiation sickness was investigated. The pharmacological properties and mechanisms of radioprotective action of nafazoline were clarified based on the dynamics of activity of erythrocytes SOD in intact and irradiated animals with the dose of 7,4 Gy. Results. The superoxide dismutase activity was found to increase significantly 60 min after single intramuscular administration of nafazolin at a dose of 5 mg/kg. Under experimental conditions of acute radiation disease modeling, a decrease in superoxide dismutase activity was observed within the first hour after exposure, evidencing the direct involvement of the antioxidant system components in the inactivation of free-radical reaction products. Conclusion. The radioprotective properties of naphazoline may be due not only to reduction of oxygen delivery to the cells of radiosensitive tissues and inhibition of their metabolism by effect on 2-adreno- and imidazoline receptors, but also by activation of antioxidant system links.

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Adachi, Tadafumi, Dean M. Robinson, Gareth B. Miles, and Gregory D. Funk. "Noradrenergic modulation of XII motoneuron inspiratory activity does not involve α2-receptor inhibition of the Ih current or presynaptic glutamate release." Journal of Applied Physiology 98, no. 4 (April 2005): 1297–308. http://dx.doi.org/10.1152/japplphysiol.00977.2004.

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Norepinephrine has powerful and diverse modulatory effects on hypoglossal (XII) motoneuron activity, which is important in maintaining airway patency. The objective was to test two hypotheses that α2-adrenoceptor-mediated, presynaptic inhibition of glutamatergic inspiratory drive (Selvaratnam SR, Parkis MA, and Funk GD. Brain Res 805: 104–115, 1998) and postsynaptic inhibition of the hyperpolarization-activated inward current ( Ih) (Parkis MA and Berger AJ. Brain Res 769: 108–118, 1997) modulate XII inspiratory activity. Nerve and whole cell recordings were applied to rhythmic medullary slice preparations from neonatal rats ( postnatal days 0–4) to monitor XII inspiratory burst amplitude and motoneuron properties. Application of an α2-receptor agonist (clonidine, 1 mM) to the XII nucleus reduced inspiratory burst amplitude to 71 ± 3% of control but had no effect on inspiratory synaptic currents. It also reduced the Ih current by ∼40%, but an Ih current blocker (ZD7288), at concentrations that blocked ∼80% of Ih, had no effect on inspiratory burst amplitude. The clonidine inhibition was unaffected by the GABAA antagonist (+)bicuculline but attenuated by the α2-antagonist rauwolscine and the imidazoline 1 (I1) antagonist efaroxan. The I1 agonist rilmenidine, but not the α2-agonist UK14304, inhibited XII output. Clonidine also reduced action potential amplitude or impaired repetitive firing. Although a contribution from α2, and in particular I1, receptors remains possible, results demonstrate that 1) noradrenergic modulation of XII inspiratory activity is unlikely to involve α2-receptor-mediated presynaptic inhibition of glutamate release or modulation of Ih; 2) inhibition of repetitive firing is a major factor underlying the inhibition of XII output by clonidine; and 3) Ih is present in neonatal XII motoneurons but does not contribute to shaping their inspiratory activity.

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Mayorov, Dmitry N., and Geoffrey A. Head. "Influence of rostral ventrolateral medulla on renal sympathetic baroreflex in conscious rabbits." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 280, no. 2 (February 1, 2001): R577—R587. http://dx.doi.org/10.1152/ajpregu.2001.280.2.r577.

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Previous studies with anesthetized animals have shown that the pressor region of the rostral ventrolateral medulla (RVLM) is a critical site in vasomotor control. The aim of this study was to develop, in conscious rabbits, a technique for microinjecting into the RVLM and to determine the influence of this area on renal sympathetic nerve activity (RSNA) and arterial pressure (AP) using local injections of glutamate, rilmenidine, ANG II and sarile. Rabbits were implanted with guide cannulas for bilateral microinjections into the RVLM ( n = 7) or into the intermediate ventrolateral medulla (IVLM, n = 6) and an electrode for measuring RSNA. After 7 days of recovery, injections of glutamate (10 and 20 nmol) into the RVLM increased RSNA by 81 and 88% and AP by 17 and 25 mmHg, respectively. Infusion of glutamate (2 nmol/min) into the RVLM increased AP by 15 mmHg and the RSNA baroreflex range by 38%. By contrast, injection of the imidazoline receptor agonist rilmenidine (4 nmol) into the RVLM decreased AP by 8 mmHg and the RSNA baroreflex range by 37%. Injections of rilmenidine into the IVLM did not alter AP or RSNA. Surprisingly, treatments with ANG II (4 pmol/min) or the ANG II receptor antagonist sarile (500 pmol) into the RVLM did not affect the resting or baroreflex parameters. Infusion of ANG II (4 pmol/min) into the fourth ventricle increased AP and facilitated the RSNA baroreflex. Our results show that agents administered via a novel microinjecting system for conscious rabbits can selectively modulate neuronal activity in circumscribed regions of the ventrolateral medulla. We conclude that the RVLM plays a key role in circulatory control in conscious rabbits. However, we find no evidence for the role of ANG II receptors in the RVLM in the moment-to-moment regulation of AP and RSNA.

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Kalapko, O. M., S. Yu Shtrygol’, S. Yu Shtrygol’, B. V. Paponov, B. V. Paponov, S. V. L’vov, and S. V. L’vov. "Investigation of the role of i1- and i2-imidazoline receptors in the mechanіsm of the hypoglycemic action of n,n’-(ethane-1,2 dyyil)bis(quinoline- 2-carboxamide)." Vìsnik farmacìï, no. 3(79) (September 12, 2014): 74–77. http://dx.doi.org/10.24959/nphj.14.1970.

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Herrera-Arizmendi, José Luis, Everardo Curiel-Quesada, José Correa-Basurto, Martiniano Bello, and Alicia Reyes-Arellano. "Effect of New Analogs of Hexyloxy Phenyl Imidazoline on Quorum Sensing in Chromobacterium violaceum and In Silico Analysis of Ligand-Receptor Interactions." Journal of Chemistry 2020 (February 25, 2020): 1–18. http://dx.doi.org/10.1155/2020/8735190.

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The increasing common occurrence of antibiotic-resistant bacteria has become an urgent public health issue. There are currently some infections without any effective treatment, which require new therapeutic strategies. An attractive alternative is the design of compounds capable of disrupting bacterial communication known as quorum sensing (QS). In Gram-negative bacteria, such communication is regulated by acyl-homoserine lactones (AHLs). Triggering of QS after bacteria have reached a high cell density allows them to proliferate before expressing virulence factors. Our group previously reported that hexyloxy phenylimidazoline (9) demonstrated 71% inhibitory activity of QS at 100 μM (IC50 = 90.9 μM) in Chromobacterium violaceum, a Gram-negative bacterium. The aim of the present study was to take 9 as a lead compound to design and synthesize three 2-imidazolines (13–15) and three 2-oxazolines (16–18), to be evaluated as quorum-sensing inhibitors on C. violaceum CV026. We were looking for compounds with a higher affinity towards the Cvi receptor of this bacterium and the ability to inhibit QS. The binding mode of the test compounds on the Cvi receptor was explored with docking studies and molecular dynamics. It was found that 8-pentyloxyphenyl-2-imidazoline (13) reduced the production of violacein (IC50 = 56.38 μM) without affecting bacterial growth, suggesting inhibition of quorum sensing. Indeed, compound 13 is apparently one of the best QS inhibitors known to date. Molecular docking revealed the affinity of compound 13 for the orthosteric site of N-hexanoyl homoserine lactone (C6-AHL) on the CviR protein. Ten amino acid residues in the active binding site of C6-AHL in the Cvi receptor interacted with 13, and 7 of these are the same as those interacting with AHL. Contrarily, 8-octyloxyphenyl-2-imidazoline (14), 8-decyloxyphenyl-2-imidazoline (15), and 9-decyloxyphenyl-2-oxazoline (18) bound only to an allosteric site and thus did not compete with C6-AHL for the orthosteric site.

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