Prevention of the serotonin syndrome in rats by repeated administration of monoamine oxidase inhibitors but not tricyclic antidepressants.
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.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001933:Brain Stem / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009526:Nialamide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D008732:Methoxydimethyltryptamines; D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D009526:Nialamide