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  • Title: The influence of SK & F 64139, a phenylethanolamine-N-methyltransferase inhibitor, on centrally mediated cardiovascular effects of alpha-methyldopa and clonidine.
    Author: Gerold M, Haeusler G.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1982 Dec; 321(4):276-81. PubMed ID: 6132343.
    Abstract:
    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.
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