Effects of the antidepressant pirlindole and its dehydro-derivative on the activity of monoamine oxidase-A and on GABAA receptors.
The effects of pirlindole and dehydro-pirlindole on GABAA receptors and MAO-A activity were investigated in vitro. Pirlindole was inactive as a GABA antagonist. Dehydro-pirlindole exhibited partial and selective blockade of a subset of GABAA receptors with an EC50 of 12 microM and maximum reversal (delta Bopt) of 42%. Inhibition of rat brain and human placenta MAO-A by both compounds was much more potent (with IC50 range 0.3-0.005 microM). Their effects on MAO-A activity were partially reversible in vitro. In contrast to pirlindole, dehydro-pirlindole may act not only as MAO-A inhibitor but also as a clozapine-like selective GABAA receptor blocker, preferentially blocking a subset of GABAA receptors that are not sensitive to DMCM or Ro 5-4864.
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; D001921:Brain / Q000201:enzymology; D002227:Carbazoles / Q000494:pharmacology*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism*
D000928:Antidepressive Agents; D002227:Carbazoles; D018756:GABA Antagonists; D008996:Monoamine Oxidase Inhibitors; D018079:Receptors, GABA; C067315:3,3a-dehydropyrazidol; D008995:Monoamine Oxidase; C009830:pirlindole