Pharmacodynamics and pharmacokinetics of some hypnotic drugs in spontaneously hypertensive rats (SHR).

Hypnotic action of barbiturates (hexobaribtal, cyclobarbital-Ca, phenobarbital, barbital) chloral hydrate, glutethimide was investigated in spontaneously hypertensive Okamoto-Aoki rats (SHR). Hypnotic effect of investigated drugs was decreased in hypertensive rats comparing with normotensive animals. The decrease in the hypnotic effect was related to the increase of the threshold hypnotic dose. No changes were observed in the pharmacokinetic parameters of hexobarbital and barbital and in the rate of crossing of blood-brain barrier by the latter drug in SHR rats. The results suggested that the decrease of hypnotic activity of investigated drugs did not depend on the hypertension but they were produced by the hyposensitivity of CNS to hypnotic agents. The latter phenomenon appeared as the result of some biochemical changes in the brain tissue.