Maxwell D R, Sumpter E A
Br J Pharmacol. 1974 Mar;50(3):355-63. doi: 10.1111/j.1476-5381.1974.tb09610.x.
1 The relative potencies of methotrimeprazine, (+)-methotrimeprazine, (+/-)-10-(3-dimethylamino-2-methylpropyl)-2-valeroyl phenothiazine hydrochloride (M & B 18,706) and (+)-M & B 18,706 in reducing the pressor action of noradrenaline in the spinal cat, reducing intercollicular decerebrate rigidity, and muscle spindle afferent activity have been studied.2 Methotrimeprazine was eight times as potent as (+)-methotrimeprazine in reducing the pressor action of noradrenaline and six times as potent in reducing decerebrate rigidity. M & B 18,706 was also eight times as potent as (+)-M & B 18,706 in reducing the pressor action of noradrenaline and six times as potent in reducing decerebrate rigidity.3 For the above compounds and chlorpromazine there was a significant correlation between the effective doses for the inhibition of the pressor action of noradrenaline and for the reduction of decerebrate rigidity.4 The doses which reduced decerebrate rigidity were similar to those that reduced muscle spindle afferent discharge. It is likely that these drugs reduce decerebrate rigidity by inhibiting fusimotor activity.5 Desipramine increased decerebrate rigidity and increased spindle afferent discharge.6 It is thought that the phenothiazine derivatives studied reduce decerebrate rigidity and spindle afferent discharge by inhibiting receptors for noradrenaline in the central nervous system.
已对甲硫哒嗪、(+)-甲硫哒嗪、(±)-10-(3-二甲氨基-2-甲基丙基)-2-戊酰基吩噻嗪盐酸盐(M&B 18,706)和(+)-M&B 18,706在降低脊髓猫去甲肾上腺素升压作用、降低中脑间脑去大脑强直以及肌梭传入活动方面的相对效价进行了研究。
在降低去甲肾上腺素升压作用方面,甲硫哒嗪的效价是(+)-甲硫哒嗪的8倍,在降低去大脑强直方面是其6倍。M&B 18,706在降低去甲肾上腺素升压作用方面也是(+)-M&B 18,706的8倍,在降低去大脑强直方面是其6倍。
对于上述化合物和氯丙嗪,抑制去甲肾上腺素升压作用的有效剂量与降低去大脑强直的有效剂量之间存在显著相关性。
降低去大脑强直的剂量与降低肌梭传入放电的剂量相似。这些药物可能通过抑制肌梭运动神经活动来降低去大脑强直。
地昔帕明增加去大脑强直并增加肌梭传入放电。
据认为,所研究的吩噻嗪衍生物通过抑制中枢神经系统中的去甲肾上腺素受体来降低去大脑强直和肌梭传入放电。