General pharmacological properties of cilostazol, a new antithrombotic drug. Part I: Effects on the central nervous system.

The pharmacological effects of the new platelet aggregation inhibitor cilostazol (6-(4-(1-cyclohexyl-1 H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone, OPC-13013) on the central nervous system were studied. Cilostazol had little effect on the general behavior of mice up to a dose of 1000 mg/kg p.o. and caused disappearance of pinna reflex, alertness and startle response and slight ptosis in only one of 6 rats at a dose of 1000 mg/kg p.o. Cilostazol had little effect on spontaneous movement and motor coordination in mice and did not potentiate hexobarbital-induced hypnosis, antagonize methamphetamine-induced hypermotor activity, cause muscle relaxation or have an anticonvulsant effect. Cilostazol did not affect normal body temperature but slightly antagonized reserpine-induced hypothermia at 300 mg/kg p.o. in mice. Cilostazol did not show an analgesic effect by Haffner's method, but it did slightly inhibit acetic acid-induced writhing at doses higher than 300 mg/kg p.o. in mice. The inhibitory effect was considered to be due to its peripheral effect. Cilostazol had little effect on discriminated avoidance response in rats, EEG arousal response in rabbits or spinal reflex in cats. However, it did slightly increase the slow wave until about 2 h after administration at 1000 mg/kg p.o., but the slow-wave sleep period did not tend to persist for a long period. These results suggest that cilostazol had little effect on the central nervous system.