[Effects of suloctidil on the central and peripheral nervous systems]

The effects of suloctidil (MY103) on the central (CNS) and peripheral nervous systems were investigated with single and consecutive administration. The general behavior in mice, awareness and motor activity were slightly depressed with the dose above 300 mg/kg, p.o. of MY 103. Soft stool was also marked in the dose above 100 mg/kg, p.o. in beagles and 1000 mg/kg, p.o. in mice. In beagles, vomiting was another syndrome with 100 and 300 mg/kg, p.o. of MY 103. Spontaneous motor activity was significantly decreased after MY 103 by p.o. administration in the dose above 100 mg/kg in mice and 300 mg/kg in rats. In sleep anesthesia studies, MY 103 and iproniazid did not potentiate the effect of a subthreshold dose of barbital, but those two drugs significantly prolonged the sleeping time of pentobarbital as chlorpromazine did. No anticonvulsive effect was observed with MY 103 in chemo- and electroshock seizure tests. My 103 of 300 mg/kg, p.o. significantly decreased the acetic acid induced writhing number, but no analgesic activity was found in the Haffner's method in mice. In the rotarod test, MY 103 of 30-300 mg/kg, p.o. inhibited the motor coordination dose-dependently. MY 103 antagonized the m-amphetamine group toxicity. A cataleptogenic effect was observed following the relatively high dose of MY 103 by an i.p. route. This effect was antagonized by atropine. The spinal reflexes in the immobilized cat, and spontaneous rabbit EEG were not affected by MY 103. The conditioned avoidance response (CAR) was also not changed with MY 103 in rats. In the isolated phrenic-nerve diaphragm preparation, 10(-4)M MY 103 irreversively inhibited the muscle twitches elicited by nerve and muscle stimulation, but suloctidil at 300 micrograms/kg, i.v., did not suppress the tibialis muscle twitches in vivo. In the consecutive administration study, MY 103 suppressed the CAR in rats and prolonged the thiopental-sleeping time in an administration period-related manner. These changes disappeared rapidly after drug withdrawal. Taking these evidences together, it can be concluded that MY 103 has little effect on the CNS with single administration, but the tendency to depress the CNS was observed after the repeated administration of MY 103.