Summary
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 α-methyldopa (50 mg/kg i.v.). However, i.c.v. administration of SK & F 64139 (5 mg/kg) to conscious SHR reduced both the α-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 α-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 α1- and α2-adrenoceptors by the PNMT inhibitor.
Blockade of central α-adrenoceptors by SK & F 64139 appears to adequately explain the inhibition of the antihypertensive effects of α-methyldopa and clonidine. The present results do not support the claim (Gerkens et al. 1980) that inhibition of the central formation of α-methyladrenaline is the mechanism underlying the antagonism of α-methyldopa-induced hypotension by SK & F 64139.
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Gerold, M., Haeusler, G. The influence of SK & F 64139, a phenylethanolamine-N-methyltransferase inhibitor, on centrally mediated cardiovascular effects of α-methyldopa and clonidine. Naunyn-Schmiedeberg's Arch. Pharmacol. 321, 276–281 (1982). https://doi.org/10.1007/BF00498513
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DOI: https://doi.org/10.1007/BF00498513