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Prevention of the serotonin syndrome in rats by repeated administration of monoamine oxidase inhibitors but not tricyclic antidepressants.

I Lucki, A Frazer

Psychopharmacology January 1, 1982 DOI: 10.1007/BF00464567 via PubMed

Summary

AI-generated from the abstract

Repeated treatment of rats with monoamine oxidase inhibitors (nialamide, pargyline, and phenelzine) prevented the serotonin syndrome—a behavioral response to serotonin receptor activation—induced by direct-acting agonists 5-MeDMT or LSD, and also reduced 3H-serotonin binding in the brain stem and spinal cord. In contrast, repeated administration of tricyclic antidepressants (amitriptyline, desmethylimipramine, and chlorimipramine) or iprindole did not significantly affect either the syndrome or binding. Pretreatment with p-chlorophenylalanine blocked nialamide's effect on the syndrome caused by 5-MeDMT. These findings suggest that repeated monoamine oxidase inhibitor treatments may prevent the serotonin syndrome by reducing serotonin receptor binding sites in the brain stem and/or spinal cord.

Study at a glance

Characteristics Experimental study Peer reviewed
Population Rats
Interventions Monoamine oxidase inhibitors (nialamide pargyline phenelzine) tricyclic antidepressants (amitriptyline desmethylimipramine chlorimipramine) iprindole p-chlorophenylalanine
Citations 91
Key finding Repeated monoamine oxidase inhibitor treatments prevented the serotonin syndrome and reduced 3H-serotonin binding in the brain stem and spinal cord, whereas tricyclic antidepressants and iprindole had no significant effect.

Abstract

The serotonin syndrome, a behavioral response produced by the activation of serotonin receptors, and 3H-serotonin binding were examined after repeated treatment of rats with different types of antidepressant drugs. The serotonin syndrome was produced by the direct-acting serotonin receptor agonists 5-methoxy-N,N-dimethyltryptamine (5-MeDMT) or d-lysergic acid diethylamide (LSD). Repeated, but not acute treatment of rats with monoamine oxidase inhibitors (nialamide, pargyline, and phenelzine) prevented the serotonin syndrome in response to either 5-MeDMT or LSD and also reduced 3H-serotonin binding in the brain stem and spinal cord. Pretreatment of rats with p-chlorophenylalanine blocked the ability of nialamide treatment to inhibit the serotonin syndrome caused by 5-MeDMT. By contrast, neither the serotonin syndrome or 3H-serotonin binding was affected significantly by the repeated administration of tricyclic antidepressants (amitriptyline, desmethylimipramine, and chlorimipramine) or iprindole. Repeated monoamine oxidase inhibitor treatments may prevent the serotonin syndrome by causing a reduction of 3H-serotonin receptor binding sites in the brain stem and/or spinal cord.

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