Effects of co-administration of a monoamine oxidase inhibitor and a 5-HT1A receptor antagonist on 5-hydroxytryptamine cell firing and release.
We report the effects of the monoamine oxidase inhibitor, tranylcypromine, combined with the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl cyclohexanecarboxamide (WAY 100635), on both 5-hydroxytryptamine (5-HT) cell firing and cortical extracellular 5-HT in the rat. Tranylcypromine inhibited 5-HT cell firing in the dorsal raphe nucleus dose-dependently (ED50 5 mg/kg i.v.). In microdialysis experiments, tranylcypromine (5 mg/kg i.v.) increased extracellular 5-HT in the frontal cortex. WAY 100635 (0.1 mg/kg i.v.) both reversed the inhibition of 5-HT cell firing and facilitated the increase in extracellular 5-HT. In conclusion, WAY 100635 enhances the effect of tranylcypromine on presynaptic 5-HT function. These data are relevant to clinical evidence that co-therapy with a 5-HT1A receptor antagonist improves the antidepressant efficacy of a monoamine oxidase inhibitor.
Sharp
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University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, UK.
Gartside
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Umbers
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004357:Drug Synergism; D004594:Electrophysiology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014191:Tranylcypromine / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D012701:Serotonin; D014191:Tranylcypromine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide