Characteristics of the GABA-potentiating action of harman

Komissarov, I. V.; Абрамец, И. И.

doi:10.1007/bf00827206

Cited by 3 publications

(3 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, possible involvement of α 2 adrenergic receptors in antinociceptive effect of ethanol and nicotine needs further investigation. Moreover, agmatine and harmane also act on NMDA and GABA A receptors , respectively, and hence the contribution of these targets could not be ruled out and needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Participation of central imidazoline binding sites in antinociceptive effect of ethanol and nicotine in rats

Aglawe¹,

Taksande²,

Kuldhariya³

et al. 2013

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

Despite synergistic morbidity and mortality, concomitant consumption of alcohol and tobacco is increasing, and their antinociceptive effect has been linked with co-abuse. Present study was designed to investigate the role of imidazoline binding sites in the antinociceptive effect of nicotine, ethanol, and their combination. Separate group of male Sprague-Dawley rats (200-250 g) were treated with different doses of alcohol (0.50-2 g/kg, i.p.) or nicotine (0.25-1 mg/kg, i.p.), and their combination evaluated in tail flick test. Influence of endogenous imidazoline binding site ligands, agonist, and antagonists were determined by their prior treatment with effective or subeffective doses of either ethanol or nicotine. Ethanol, nicotine, or their subeffective dose combination exhibited significant antinociceptive effects in dose-dependent manner. Antinociceptive effect of ethanol and nicotine was significantly augmented by intracerebroventricular (i.c.v.) administration of endogenous imidazoline receptor ligands, harmane (25 μg/rat, i.c.v.) and agmatine (10 μg/rat, i.c.v.), as well as imidazoline I1 /α2 adrenergic receptor agonist, clonidine (2 μg/rat, i.c.v.), I1 agonist moxonidine (25 μg/rat, i.c.v.), and imidazoline I2 agonist, 2-BFI (10 μg/rat, i.c.v.). Conversely, antinociception elicited by ethanol or nicotine or their subeffective dose combination was antagonized by pretreatment with imidazoline I1 antagonist, efaroxan (10 μg/rat, i.c.v.), and I2 antagonist, idazoxan (4 μg/rat, i.c.v.), at their per se ineffective doses. These findings project imidazoline binding ligands as important therapeutic molecules for central antinociceptive activity as well as may reduce the co-abuse potential of alcohol and nicotine.

show abstract

Section: Discussionmentioning

confidence: 99%

Participation of central imidazoline binding sites in antinociceptive effect of ethanol and nicotine in rats

Aglawe¹,

Taksande²,

Kuldhariya³

et al. 2013

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…This modulation may, at least in part, be related to changes in the GABA receptor affinity (Lehoullier and Ticku, 1987). Harmane has a GABA-potentiating effect due to its main action on chloride ionophores coupled with the GABA receptor (Komissarov and Abramets, 1982). A probable mechanism for memory impairment induced by administration of harmane and muscimol might be due to the binding of harmane to the GABA receptor complex.…”

Section: Discussionmentioning

confidence: 99%

Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task

Nasehi

Morteza-zadeh²,

Khakpai

et al. 2016

Neuroscience

View full text Add to dashboard Cite

In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABA receptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABA receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABA receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001μg/mouse) restored, whereas muscimol (0.001μg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABA receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation.

show abstract

“…Harmane was previously proposed to be an endogenous ligand at benzodiazepine receptors (Rommelspacher et al, 1980), a site present on the GABA receptor complex (Kostowski, 1995). Harmane was shown to modulate the exocytotic release of GABA in rat brain (Dolzhenko and Komissarov, 1984;Komissarov and Abramets, 1982); illustrating direct harmane activity at these sites. Furthermore, GABA and its selective ligands were reported to influence the release of 5-HT from rat brain; illustrating the existence of GABA heteroreceptors on 5-HT terminals (Balfour, 1980;Tao et al, 1996).…”

Section: Harmanementioning

confidence: 96%