Behavioral effects of the imidazoline I2 receptor ligand BU99006 in rats

Qiu, Yanyan; Thorn, David A.; Zhang, Yanan; He, Xiaohua; Li, Jun-Xu

doi:10.1097/fbp.0000000000000028

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…Drug discrimination experiments were conducted in commercially available operant chambers within sound-attenuating, ventilated enclosures (Coulbourn Instruments Inc., Allentown, PA, USA) (Qiu et al, 2014a; Qiu et al, 2014b). Each chamber includes an open space (30.5 cm by 24.5 cm by 21.0 cm), a grid floor, and a pellet dispenser with a pellet receptacle that was centered between two response levers, above which were stimulus lights.…”

Section: Methodsmentioning

confidence: 99%

Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and phenyzoline in rats

Qiu

Zhang

2015

European Journal of Pharmacology

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Although imidazoline I2 receptor ligands have been used as discriminative stimuli, the role of efficacy of I2 receptor ligands as a critical determinant in drug discrimination has not been explored. This study characterized the discriminative stimulus effects of selective imidazoline I2 receptor ligands BU224 (a low-efficacy I2 receptor ligand) and phenyzoline (a higher efficacy I2 receptor ligand) in rats. Two groups of male Sprague-Dawley rats were trained to discriminate 5.6 mg/kg BU224 or 32 mg/kg phenyzoline (i.p.) from their vehicle in a two-lever food-reinforced drug discrimination procedure, respectively. All rats acquired the discriminations after an average of 18 (BU224) and 56 (phenyzoline) training sessions, respectively. BU224 and phenyzoline completely substituted for one another symmetrically. Several I2 receptor ligands (tracizoline, CR4056, RS45041, and idazoxan) all occasioned > 80% drug-associated lever responding in both discriminations. The I2 receptor ligand 2-BFI and a monoamine oxidase inhibitor harmane occasioned > 80% drug-associated lever responding in rats discriminating BU224. Other drugs that occasioned partial or less substitution to BU224 cue included clonidine, methamphetamine, ketamine, morphine, methadone and agmatine. Clonidine, methamphetamine and morphine also only produced partial substitution to phenyzoline cue. Naltrexone, dopamine D2 receptor antagonist haloperidol and serotonin (5-HT) 2A receptor antagonist MDL100907 failed to alter the discriminative stimulus effects of BU224 or phenyzoline. Combined, these results are the first to demonstrate that BU224 and phenyzoline can serve as discriminative stimuli and that the low-efficacy I2 receptor ligand BU224 shares similar discriminative stimulus effects with higher-efficacy I2 receptor ligands such as phenyzoline and 2-BFI.

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Section: Methodsmentioning

confidence: 99%

Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and phenyzoline in rats

Qiu

Zhang

2015

European Journal of Pharmacology

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“…BU99006 is reported to be an irreversible I 2 receptor ligand that can reduce the available I 2 receptors (Tyacke et al, 2002). However, behavioral studies show that BU99006 functions as an I 2 receptor agonist (Qiu et al, 2014b). Nevertheless, the exciting new findings as seen recently have already greatly improved our understanding of imidazoline I 2 receptor pharmacology.…”

Section: Neuropharmacology Of Imidazoline I2 Receptor Ligandsmentioning

confidence: 99%

Imidazoline I 2 receptors: An update

2017

Pharmacology & Therapeutics

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Since first introduced more than two decades ago, the research in imidazoline I2 receptors has been steadily increasing. This review provides an update on the current status of I2 receptor pharmacology. Imidazoline I2 receptors or I2 binding sites refer to several (at least four) different proteins that bind to [3H]-idazoxan and [3H]-2-BFI with high affinity. The molecular identities of the proteins remain elusive. One of the proteins (45 kD) seems to be consistent with the identity of brain creatine kinase. The biological functions of I2 receptors have been primarily unveiled by the studies of selective I2 receptor ligands. Accumulating evidence suggests that I2 receptor ligands are effective analgesics for persistent and chronic painful conditions such as inflammatory, neuropathic and postoperative pain. One selective I2 receptor ligand, CR4056, has been advanced to phase II clinical trial with the therapeutic indication of chronic inflammatory pain (osteoarthritis). The expansion to the treatment of other chronic pain conditions should be expected if CR4056 could eventually be approved as a new drug. I2 receptor ligands also demonstrate robust discriminative stimulus activity and induce a characteristic discriminative cue in animals. Biochemical and preclinical in vivo investigations also suggest that I2 receptor ligands have neuroprotective activity and modulate body temperature. The emerging discrepancies of a range of purported selective I2 receptor ligands suggest different pharmacological effects mediated by discrete I2 receptor components which likely attribute to the I2 receptor-related proteins. It is proposed that the I2 receptors represent an emerging drug target for the treatment of neurological disorders such as pain and stroke, and deserve more research attention to translate preclinical findings to pharmacotherapies.

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“…Further development will be aided by computational methods, both for structure-function relationships and for drug-like properties to ensure brain permeation (Moraes and de Azevedo, 2012, Nikolic and Agbaba, 2012, Vucicevic et al, 2015. With better understanding of the pharmacology of I 2 sites, behavioral studies are also now appearing (Qiu et al, 2014, Qiu et al, 2015.…”

Section: Molecular Properties Of Mao Bmentioning

confidence: 99%

Molecular aspects of monoamine oxidase B

Ramsay

2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Graphical abstract Highlights• MAO B activity depends on both amine and oxygen concentrations KeywordsMonoamine oxidase B; kinetics; drug design; neurotransmitter levels; platelet AbbreviationsAlzheimer's Disease, AD; Parkinson's Disease, PD; dopamine transporter, DAT; serotonin transporter, SERT; noradrenaline transporter, NET; the vesicular transporter, VMAT; Gprotein coupled receptor, GPCR; induced pluripotent stem cells, iPSC; serotonin reuptake inhibitor, SSRI; brain-derived neurotrophic factor, BDNF; multi-target designed ligands, MTDL; IC 50 , the concentration of compound required to inhibit a specified assay by 50%; K i , a kinetically measured inhibitor dissociation constant. Word count -approx 5490 (excluding references). Abstract 196 words.3

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Behavioral effects of the imidazoline I2 receptor ligand BU99006 in rats

Cited by 7 publications

References 29 publications

Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and phenyzoline in rats

Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and phenyzoline in rats

Imidazoline I 2 receptors: An update

Molecular aspects of monoamine oxidase B

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