Gerold M, Haeusler G
Naunyn Schmiedebergs Arch Pharmacol. 1982 Dec;321(4):276-81. doi: 10.1007/BF00498513.
The inhibitor of phenylethanolamine-N-methyl transferase (PNMT), SK&F 64139 (7, 8-dichloro-1, 2, 3, 4-tetrahydroisoquinoline), when given i.v. (5 mg/kg), did not prevent the decrease of blood pressure induced in conscious spontaneously hypertensive rats (SHR) by alpha-methyldopa (50 mg/kg i.v.). However, i.c.v. administration of SK&F 64139 (5 mg/kg) to conscious SHR reduced both the alpha-methyldopa- and the clonidine-induced hypotension. Bradycardia in response to clonidine was also prevented by i.c.v. SK & F 64139. When the antihypertensive effect of alpha-methyldopa or clonidine was fully established, i.c.v. administration of SK & F 64139 returned blood pressure within a few minutes to the initial value. Similarly, the bradycardia after clonidine was promptly reversed by i.c.v. SK & F 64139. In pithed rats the pressor responses to both methoxamine and clonidine were antagonized by SK & F 64139 suggesting blockade of vascular alpha 1-and alpha 2-adrenoceptors by the PNMT inhibitor. Blockade of central alpha-adrenoceptors by SK & F 64139 appears to adequately explain the inhibition of the antihypertensive effects of alpha-methyldopa and clonidine. The present results do not support the claim (Gerkens et al. 1980) that inhibition of the central formation of alpha-methyladrenaline is the mechanism underlying the antagonism of alpha-methyldopa-induced hypotension by SK & F 64139.
苯乙醇胺 - N - 甲基转移酶（PNMT）抑制剂SK&F 64139（7, 8 - 二氯 - 1, 2, 3, 4 - 四氢异喹啉）静脉注射（5毫克/千克）时，不能预防静脉注射α - 甲基多巴（50毫克/千克）引起的清醒自发性高血压大鼠（SHR）血压下降。然而，向清醒的SHR脑室内注射SK&F 64139（5毫克/千克）可降低α - 甲基多巴和可乐定引起的低血压。脑室内注射SK&F 64139还可预防可乐定引起的心动过缓。当α - 甲基多巴或可乐定的降压作用充分显现后，脑室内注射SK&F 64139可在几分钟内使血压恢复到初始值。同样，脑室内注射SK&F 64139可迅速逆转可乐定后的心动过缓。在脊髓横断大鼠中，SK&F 64139拮抗了对甲氧明和可乐定的升压反应，提示PNMT抑制剂可阻断血管α1和α2肾上腺素能受体。SK&F 64139对中枢α肾上腺素能受体的阻断似乎足以解释其对α - 甲基多巴和可乐定降压作用的抑制。目前的结果不支持Gerkens等人（1980年）的观点，即抑制α - 甲基肾上腺素的中枢形成是SK&F 64139拮抗α - 甲基多巴诱导的低血压的机制。
