| Interactions of a non-selective monoamine oxidase inhibitor, phenelzine, with inhibitors of 5-hydroxytryptamine, dopamine or noradrenaline re-uptake. | |
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MedLine Citation:
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PMID: 6747915 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Interactions of combined antidepressants which occur in man were reproduced in rats pretreated with phenelzine, features elicited including myoclonic phenomena, an augmented lower limb flexor reflex, muscle fasiculation and fatalities, particularly with combinations incorporating 5-hydroxytryptamine (5-HT) re-uptake inhibitors. Combinations of antidepressants included phenelzine with 5-HT re-uptake inhibitors (paroxetine, fluoxetine, clomipramine); with "mixed" re-uptake inhibitors affecting 5-HT and noradrenaline (imipramine, amitriptyline); with noradrenaline re-uptake inhibitors (desipramine, maprotiline, nisoxetine) and with dopamine re-uptake inhibitors (benztropine, nomifensine). Myoclonic phenomena such as forelimb flexor-extensor movements, head and body twitches, occurred in phenelzine pretreated rats after paroxetine, fluoxetine, clomipramine, imipramine, amitriptyline and desipramine. Wet dog shakes, the most intense phenomenon, were obtained only after paroxetine, fluoxetine, clomipramine and imipramine. Myoclonic features were prevented when pretreatment included p-chlorophenylalanine but were unaffected when this incorporated alpha-methyl-p-tyyrosine; there were attenuated by methysergide, cyproheptadine, clozapine or pimozide. The myoclonic phenomena were reproduced by combination of 5-hydroxytryptophan but not L-3,4-dihydroxyphenylalanine with clomipramine. Electrocortical changes observed included 2-4 Hz, 5-8 Hz, large amplitude potentials unrelated to the myoclonic incidents and unaffected by sensory stimulation. Following phenelzine, brain monoamine oxidase (MAO) A inhibition was 99% and that of MAO B, 88%; 5-HT concentration was significantly elevated in the cortex and hypothalamus, as was hypothalamic noradrenaline. Peak and basal tensions of a lower-limb flexor reflex were elevated in phenelzine pretreated spinal rats by fluoxetine, paroxetine, clomipramine and imipramine, effects attenuated by cyproheptadine. Forelimb flexor-extensor movements and body twitches were elicited by fluoxetine and paroxetine in phenelzine pretreated spinal rats in the presence of electrical stimulation of the central stump of a divided posterior tibial nerve. Pressor responses were observed in phenelzine pretreated spinal rats given 5-HT re-uptake inhibitors, "mixed" re-uptake inhibitors and those affecting noradrenaline re-uptake; ECG anomalies occurred in such rats given clomipramine. |
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Authors:
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E Marley; K M Wozniak |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of psychiatric research Volume: 18 ISSN: 0022-3956 ISO Abbreviation: J Psychiatr Res Publication Date: 1984 |
Date Detail:
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Created Date: 1984-09-12 Completed Date: 1984-09-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376331 Medline TA: J Psychiatr Res Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 173-89 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antidepressive Agents, Tricyclic / pharmacology* Brain Chemistry / drug effects Dopamine Antagonists* Drug Interactions Male Monoamine Oxidase Inhibitors / pharmacology Motor Activity / drug effects Myoclonus / chemically induced Norepinephrine / antagonists & inhibitors* Phenelzine / pharmacology* Rats Rats, Inbred Strains Serotonin Antagonists / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Antidepressive Agents, Tricyclic; 0/Dopamine Antagonists; 0/Monoamine Oxidase Inhibitors; 0/Serotonin Antagonists; 51-41-2/Norepinephrine; 51-71-8/Phenelzine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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