Effects of cadralazine on the central nervous system]

The effect of cadralazine, a new antihypertensive agent, were studied on the central nervous systems in experimental animals. Oral administration of 0.5 mg/kg or more of cadralazine depressed spontaneous motor activity and enhanced electroshock-induced convulsions in mice. The drug produced flush on the tail or ears at 0.5 mg/kg, p.o. or more and enhanced respiratory movement at 5.0 mg/kg, p.o. or more in rats. At 2.5 mg/kg, p.o., cadralazine prolonged the thiopental-sleeping time and inhibited methamphetamine-induced hypermotility as well as acetic acid-induced writhing in mice. Pretreatment of naloxone, however, failed to antagonize this inhibitory effect on acetic acid-induced writhing. Cadralazine at 5.0 mg/kg, p.o., lowered body temperature in rats. This same dose antagonized tremorine-induced behaviors in mice. Cadralazine at a dose of 1.0 or 5.0 mg/kg, i.v., had no effect on the spontaneous EEG pattern and the threshold of arousal EEG response induced by electrical stimulation to the midbrain reticular formation in rabbits. Even at a dose as large as 100 mg/kg, p.o., the drug showed no significant effect on the following effects: conditioned avoidance response in rats, spinal reflex in cats, tail pinch-induced pain in mice, and somatic function in the inclined screen or in the traction test in mice. In conclusion, cadralazine, having no passage through the blood-brain barrier, showed several pharmacological actions on behaviors. These actions are considered to be derived from its vasodilative properties and were qualitatively similar to those of hydralazine.