Effects of the antidepressant pirlindole and its dehydro-derivative on the activity of monoamine oxidase-a and on GABAA receptors |
| |
| Authors: | A. E. Medvedev V. I. Shvedov T. M. Chulkova O. A. Fedotova E. Saederup R. F. Squires |
| |
| Affiliation: | (1) Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia;(2) Centre of Drug Chemistry, Institute of Pharmaceutical Chemistry, Moscow, Russia;(3) Nathan Kline Institute for Psychiatric Research, 140 Old Organgeburg Rd., 10962 Orangeburg, NY |
| |
| Abstract: | 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 12μM and maximum reversal (ΔBopt) 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 μM). 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. Pirlindole is the generic name of the drug pyrazidol. |
| |
| Keywords: | Pirlindole dehydroperlindole clozapine antidepresant/antipsychotic monoamine oxidase GABA receptors |
| 本文献已被 SpringerLink 等数据库收录！ |
