[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.
Nishimori
T
T
Biological Research Center for the Protection of Environment, Shiga, Japan.
Morino
K
K
Tsuchiyama
M
M
Ikeda
H
H
Hasegawa
K
K
Higashio
T
T
Akita
S
S
Yamauchi
T
T
Nakao
K
K
Inukai
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects*; D005260:Female; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D011724:Pyridazines; D006830:Hydralazine; C031877:cadralazine