The administration of 2,2′,2″-tripyridine produced generalized tremor, myoclonus, and hindlimb abduction, similar to the "5-hydroxytryptamine (5-HT) syndrome," in mice. Pretreatment with mianserin, cyproheptadine, methysergide, or metergoline ameliorated, whereas 5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), or 8-hydroxy-2-[di-n-propylamino]tetraline hydrobromide (8-OH-DPAT) augmented the 2,2′,2″-tripyridine-induced tremor. Furthermore, diazepam and flunitrazepam exhibited a dose-dependent protection against 2,2′,2″-tripyridine-induced tremor in mice, but pentobarbital only had a slightly protective effect. The inhibitory effects of diazepam and flunitrazepam on the 2,2′,2″-tripyridine-induced tremor were potentiated in mice pretreated with p-chlorophenylalanine (PCPA). These observations suggest a serotonin-mediated action of 2,2′,2″-tripyridine in its tremor action and that the benzodiazepine agonist attenuation of the 2,2′,2″-tripyridine-induced tremor is probably mediated through the GABAergic inhibition of serotonergic neurons.
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