Tremorogenesis by LON-954 [N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride]: evidence for the involvement of 5-hydroxytryptamine.

LON-954 [N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride], a novel tremorogen known to affect the central dopaminergic system, has been investigated in rats for tremor and 5-hydroxytryptamine (5-HT) metabolism. Five, 10 and 20 mg/kg of LON-954 IP caused a reproducible and consistent tremor with a high frequency (16 Hz) within 2 minutes and lasting 30-45 minutes. 5-HT content of the tuberculum olfactorium and basal ganglia was found to be increased significantly at a time when 5-hydroxyindoleacetic acid (5-HIAA) content showed a decrease. 5-HT and 5-HIAA of medulla oblongata showed significant changes only after 15 minutes. The alterations in the levels of the indoleamine in tuberculum olfactorium and its relationship with dosage as well as duration and intensity of LON-954 tremor indicate the involvement of the mesolimbic system in its action. A direct role of 5-HT in LON-tremor was evidenced since the drug failed to produce tremor in rats pretreated with p-chlorophenylalanine (300 mg/kg IP) for 3 days.