Behavioral, toxic, and neurochemical effects of sydnocarb, a novel psychomotor stimulant: Comparisons with methamphetamine

Sydnocarb (3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine) is a psyc hostimulant in clinical practice in Russia as a primary and adjunct therapy for a host of psychiatric disorders, including schizophrenia and depressio n. It has been described as a stimulant with an addiction liability and tox icity less than that of amphetamines. The present study undertook to evalua te the psychomotor stimulant effects of sydnocarb in comparison to those of methamphetamine. Sydnocarb increased locomotor activity of mice with reduc ed potency (similar to 10-fold) and efficacy compared with methamphetamine. Sydnocarb blocked the locomotor depressant effects of haloperidol at doses that were inactive when given alone. The locomotor stimulant effects of bo th methamphetamine and sydnocarb were dose-dependently blocked by the dopam ine D1 and D2 antagonists SCH 39166 and spiperone, respectively; blockade g enerally occurred at doses of the antagonists that did not depress locomoto r activity when given alone. In mice trained to discriminate methamphetamin e from saline, sydnocarb fully substituted for methamphetamine with a 9-fol d lower potency. When substituted for methamphetamine under self-administra tion experiments in rats, 10-fold higher concentrations of sydnocarb mainta ined responding by its i.v, presentation. Sydnocarb engendered stereotypy i n high doses with approximately a 2-fold lower potency than methamphetamine . However, sydnocarb was much less efficacious than methamphetamine in indu cing stereotyped behavior. Both sydnocarb and methamphetamine increased dia lysate levels of dopamine in mouse striatum; however, the potency and effic acy of sydnocarb was less than methamphetamine. The convulsive effects of c ocaine were significantly enhanced by the coadministration of nontoxic dose s of methamphetamine but not of sydnocarb. Taken together, the present find ings indicate that sydnocarb has psychomotor stimulant effects that are sha red by methamphetamine while demonstrating a reduced behavioral toxicity.