Michitada Sasajima

[Studies on the physical dependence liability of chlorphenesin carbamate (author's transl)].

Physical dependence liability of chlorphenesin carbamate (CPC) was studied in parallel with phenobarbital-Na (PB). Beagle dogs were used and the overall duration of the experiment was 85 days, i.e. the first dosing period was 42 dyas (6 weeks) in which drugs were repeatedly administered orally once daily, followed by a withdrawal period (7 days), the second dosing period was continued from the 50th-78th day in which the form and schedule of drug administration was as in the first dosing period. The last 79th to 85th days were used for substitution experiments. In both dosing periods, PB but not CPC showed signs of tolerance formation. Severe withdrawal syndrome was observed in PB administered dogs whereas there were no changes of behavior observed in CPC-dogs by withdrawal and substitution procedures, respectively. CPC apparently does not have a physical dependence liability.

Effect of dopamine on perfusion pressure in rat peripheral blood vessels

Rat mesenteric and hind limb arteries were perfused with the rats own blood under constant perfusion rate, in situ. The effect of dopamine (DA) administered intraarterially was investigated and compared with effects of norepinephrine (NE), tyramine (Tyr), and phenylephrine (PHE). The magnitude of the vasoconstrictive maximum response of both vasculatures to NE and PHE was larger than those to DA and Tyr, and those to DA were larger than those to Tyr in hind limb, but those to Tyr were more potent than those to DA in the mesenteric artery. The vasoconstriction evoked by celiac ganglionic stimulation was much the same to that evoked by NE and PHE. Under cocaine infusion, the rise in perfusion pressure of both vasculatures evoked by NE and PHE. Under cocaine infusion, the rise in perfusion pressure of both vasculatures evoked by NE was slight, but the duration was markedly potentiated. However, the effect of Tyr was suppressed and that of DA was not changed. In rats on alpha-methyl-rho-tyrosine, the responses of both vasculatures to Tyr were reduced and those to NE and DA were not changed. In the reserpinized rat, the effect of NE was not changed and that of Tyr was reduced, while that of D was more evident in both vasculatures. After phenoxybenzamine treatment, vasoconstrictive effect of DA was reversed in mesenteric and reduced in hind limb artery. Vasodilating effect of DA after phenoxybenzamine, was not changed by treatment with propranolol, atropine, and diphenhydramine but was reduced with reserpine and abolished with haloperidol. These results suggest that the vasoconstrictive effect of DA depends partly on indirect sympathomimetic action, and after phenoxybenzamine, DA acts by vasodilating the DA receptor. Potentiation with reserpine may depend on a post-synaptic mechanism and increase in dopamine-beta-hydroxylase activity.

Effects of dopamine on the isolated left atrium of the rat

摘出ラット左心房標本におけるdopamineの効果をreserpine，cocaine，6-hydroxy-dopamine，LiClの処理下で，norepinephrine，tyramineの効果と比較検討した．1)Reserpine処理下ではnorepinephrineの効果は変化せず，tyramine，dopamineの効果は抑制された．2)Reserpine+cocaine処理下ではnorepinephrine，dopanlineに対する心房の閾値はさがり有意に増強された．3)6-hydroxydopamine処理ではnorepinephrineの効果は有意に増強され，tyramineの効果は抑制されたが，dopamineの効果は変化しなかった．4)LiClの処理下ではnorepinephrine，tyramine，dopamineの効果は同様に抑制された．以上の結果より，dopamineのラット左心房に対する作用はいわゆる“mixedtype”によるものと考えられ，これに対するLiClの効果はnorepinephrine，tyramineに対する結果と差はないことから後膜側の抑制が主であると考えられる．