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 microM) than that of GABAA receptors. Pirlindole was inactive as a GABA antagonist. Dehydro-pirlindole exhibited selective blockade of GABA-A receptors with EC50 12 microM. 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.
Medvedev
A E
AE
Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia.
Shvedov
V I
VI
Chulkova
T M
TM
Fedotova
O A
OA
Saederup
E
E
Squires
R F
RF
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000201:enzymology; D002227:Carbazoles / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D000928:Antidepressive Agents; D001570:Benzodiazepinones; D002227:Carbazoles; D002243:Carbolines; D018756:GABA Antagonists; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011963:Receptors, GABA-A; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; C028513:4'-chlorodiazepam; C067315:3,3a-dehydropyrazidol; D008995:Monoamine Oxidase; D003024:Clozapine; C009830:pirlindole