The influence of the antidepressant pirlindole and its dehydro-derivative on the activity of monoamine oxidase A and GABAA receptor binding
The influence of pirlindole and dehydro-pirlindole on GABAA receptor binding and MAO-A activity was investigated in vitro. Inhibition of rat brain and human placenta MAO-A by both compounds was much more potent (with IC50 range 0.3–0.005 μM) than that of GABAA receptors. Pirlindole was inactive as a GABA antagonist. Dehydro-pirlindole exhibited selective blockade of GAB A-A receptors with EC50 12 μM. Effects of both compounds on MAO-A activity were partially reversible. Data obtained suggest that in contrast to pirlindole dehydro-pirlindole may act not only as a MAO-A inhibitor but also as a potent GABAA receptor blocker.
KeywordsGABAA Receptor Monoamine Oxidase Biomedical Chemistry Gaba Antagonist TBPS Binding
Unable to display preview. Download preview PDF.
- Anderson M, Tipton KF (1994) Estimation of monoamine oxidase concentration in soluble and membrane-bound preparations by inhibitor binding. J Neural Transm [Suppl] 41: 47–53Google Scholar
- Baumanis EA, Birska IA, Reikhman GO, Shvedov VI, Gorkin VZ (1987) On the mechanism of modification by pyrazidol of the catalytic activity of mitochondrial monoamine oxidase. Probl Med Chem N6: 90–96Google Scholar
- Dvoryantseva GG, Pol’shakov VI, Sheikner Yu N, Shvedov VI, Grynev AN, Mashkovsky MD, Karapetyan HA, Strukov YT (1985) Structure-activity relationship in pyrazino[3,2, l-j,k] carbazole derivatives. Eur J Med Chem-Chem Ther 230: 414–418Google Scholar
- Gorkin VZ (1985) Studies on the nature and specific inhibition of monoamine oxidases. In: Kelemen K, Magyar K, Vizi ES (eds) Neuropharmacology-85. Akademiai Kiado, Budapest, pp 9–14Google Scholar
- Kuksgaus NE, Golovina SM, Adnreeva NI (1991) The influence of the Soviet antidepressants pyrazidol and incazan on the effect of Clonidine. Farmacol Toksikol 54(1): 11–14Google Scholar
- Martorana PA, Heucke O, Nitz R-E (1979) The new antidepressant pirlindole. Antagonism of acute overdose in the mouse. Arzneimittelforschung/Drug Res 29: 950–952Google Scholar
- Mashkovsky MD (1993) Drugs: reference book for clinicians, vol 1. Meditzina, Moscow, pp 110–116Google Scholar
- Mashkovsky MD, Gorkin VZ, Veryovkina IV, Asnina VV, Tupikina SM (1981) Selective inhibition of type A monoamine oxidase by pyrazidol. Buyl Eksper Biol Med N2: 169–171Google Scholar
- Singer TP (1985) Inhibitors of FAD-containing monoamine oxidases. In: Mondovi B (ed) Structure and funcitons of amine oxidases. CRC Press, Boca Raton, pp 219–229Google Scholar
- Verstakova OL, Gerchikov LN, Chicherina LA, Sharova SA, Liberman SS (1985) Toxi-cological characteristics of the Soviet antidepressant pyrazidol. Farmacol Toksikol 48: 57–60Google Scholar