Pharmacological effects of the antianxiety compound suriclone and its principal metabolites

The pharmacodynamic effects of 4-methyl-1-piperazinecarboxylic acid ester with (+/-)-6-(7-chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-7-h ydr oxy-5H-p- dithiino[2,3-c]pyrrol-5-one (suriclone, RP-31264) and its principal metabolites M1 and M2 on respiration, cardiovascular system, autonomic nervous system, smooth muscle and other physiological parameters were investigated in various animal species. Suriclone, 1 mg/kg i.v., increased the amplitude of respiratory movement, decreased the respiratory rate and blood pressure and increased the heart rate in conscious rabbits. The respiratory and depressor effects were more evident in pentobarbital anesthetized rabbits. In anesthetized dogs, suriclone, 0.05 or 0.5 mg/kg i.v., produced essentially the same effects as seen in the anesthetized rabbits. The ECG pattern was not significantly changed in any animal. Such effects on respiration and on the cardiovascular system of metabolites M1 and M2 in the rabbits were weak. In the isolated guinea-pig atria, suriclone, 10(-6) g/ml, had no effect but increased contractility and decreased heart rate at a high concentration of 10(-5) g/ml. Both M1 and M2 had weak effects. Suriclone had no action on flow rate of the perfusate through the blood vessels of the isolated rabbit ear. In anesthetized dogs, suriclone 0.5 mg/kg i.v., did not affect the responses to vagal stimulation or to pre- and postganglionic stimulation of cardiac ganglion. Suriclone instilled onto the eye or i.v. had no appreciable effect on pupillary diameter or the miotic response in rabbits, but an abnormal oculogyration was evoked when the drug was given i.v. at 1 mg/kg. M1 or M2 had no such effect. Suriclone did not exert analgesic effects in mice.(ABSTRACT TRUNCATED AT 250 WORDS)