Comparative study of pirlindole, a selective RIMA, and its two enantiomers using biochemical and behavioural techniques
| Autor: | C. Lejeune, E. Chleide, E. Decamp, Albert Dresse, J. Delarge, Pascal De Tullio, Jean-François Liégeois, Jean Gerardy, Jacques Damas, J. Geczy, J. Bruhwyler |
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| Rok vydání: | 1998 |
| Předmět: |
Monoamine Oxidase Inhibitors
Reserpine Carbazoles Hypothermia Pharmacology Mice chemistry.chemical_compound medicine Animals Blepharoptosis Rats Wistar Monoamine Oxidase IC50 biology Chemistry Brain Pirlindole Stereoisomerism Antidepressive Agents In vitro Rats Psychiatry and Mental health biology.protein Female Enantiomer Monoamine oxidase A medicine.symptom Ex vivo Behavioural despair test |
| Zdroj: | Behavioural Pharmacology. 9:731-737 |
| ISSN: | 0955-8810 |
| DOI: | 10.1097/00008877-199812000-00008 |
| Popis: | The interaction with monoamine oxidase A (MAO-A) and B has been shown to be sensitive to the absolute configuration of molecules. Therefore, the aim of this study was to compare the effects of the racemic pirlindole (a selective and reversible MAO-A inhibitor) and its two enantiomers using biochemical techniques (in vitro and ex vivo determination of rat brain MAO-A and MAO-B activity) and behavioural models (forced swimming test and reserpine-induced hypothermia and palpebral ptosis test). In vitro, the MAO-A IC50 of (+/-)-pirlindole, R-(-)-pirlindole and S-(+)-pirlindole were 0.24, 0.43 and 0.18 microM, respectively. Ex vivo, their ID50 were 24.4, 37.8 and 18.7 mg/kg i.p. The differences between the three compounds were not significant, with a ratio between the two enantiomers [R-(-)/S-(+)] of 2.2 in vitro and 2.0 ex vivo. MAO-B was only slightly inhibited. In the forced swimming test and the reserpine-induced hypothermia and ptosis model, the three compounds had an antidepressant profile. In the forced swimming test, the minimal effective dose ratio between the R-(-) and the S-(+) was again around 2.0. The behavioural observations were thus clearly in accordance with the biochemical data. |
| Databáze: | OpenAIRE |
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