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本文报导了18个氯丙嗪裂环类似物的神经药理作用。試驗結果表明:按(Ⅰ)所示虛线剖裂吩噻嗪(即苯噻嗪,phenothiazine)环系后,它們的鎮靜鎮定作用消失,抗組織胺作用明显減弱,局部麻醉作用有所增强。其中N-(β-对-氯苯硫乙基)N-(β-哌啶基丙酰基)-苯胺盐酸盐(NM-568)的局部麻醉效能更为明显,用多种方法与沙夫卡因和普魯卡因比較試驗,获得它們的局部麻醉效价比例如下:(1)家兔角膜試驗:NM-568的表面麻醉效力約接近沙夫卡因,較普魯卡因强1060倍。(2)豚鼠皮內丘样試驗:普魯卡因的效价为1;NM-568,27.5;沙夫卡因,22。(3)小白鼠坐骨神經传导阻滞試驗:如以普魯卡因的效价为1;NM-568,16;沙夫卡因,39.(4)蟾蜍脊髓麻醉:普魯卡因的效价为1;NM-568,9;沙夫卡因,8。对小白鼠的急性毒性,NM-568較沙夫卡因約小1倍,比普魯卡因約大3倍;它对家兔皮內注射和角膜的刺激作用較普魯卡因和沙夫卡因大。氯丙嗪按上列方式裂环后,发現N-(β-对-氯苯硫乙基)N-(γ-嗎啉基)-苯胺盐酸盐(NM-572),N-(β-对-氯苯硫乙基)N-(γ-哌啶基丙基)-苯胺盐酸盐(NM-578)在較大剂量时有抗电休克作用,但作用持續时间仅2小时。
This article reports the neuropharmacological effects of 18 chlorpromazine split ring analogues. The results showed that the sedation and stabilization of the phenothiazine rings were disappeared when the phenothiazine ring was broken according to the dotted line in (Ⅰ). The antihistamine effect was obviously weakened and the local anesthetic effect was enhanced. Among them, the local anesthetic efficacy of N- (p-chlorophenylthioethyl) N- (β-piperidinylpropionyl) -aniline hydrochloride (NM-568) was more obvious. Comparison of caffeine and procaine to obtain their local anesthetic titers are as follows: (1) rabbit corneal test: NM-568 surface anesthetic potency close to the sulfucaine, stronger than procaine 1060 times . (2) Hypothalamus test in guinea pigs: Procaine titer was 1; NM-568, 27.5; (3) Sciatic nerve conduction block test in mice: if the potency of procaine is 1; NM-568,16; and Sulphacin, 39. (4) Toad spinal anesthesia: procaine potency 1; NM-568,9; and Sulphacin, 8. In acute toxicity to mice, NM-568 is about 1 time smaller than that of dibucaine and about 3 times larger than procaine; it stimulates the intracranial injection and corneal stimulation in rabbits more than procaine and sfka Because of big. After chlorpromazine cleavage in the above manner, N- (p-chlorophenylthioethyl) N- (? -morpholino) -aniline hydrochloride (NM- 572) (P-chlorophenylthioethyl) N- (γ-piperidinylpropyl) -aniline hydrochloride (NM-578) has an anti-shock effect at higher doses but for a duration of only 2 hours.