?-Monofluoromethyldopa (MFMD) in combination withl-DOPA

Abstract

We have investigated the interaction of α-monofluoromethyldopa (MFMD) with the effects of i.p. injectedl-DOPA (200 mg·kg⁻¹) on blood pressure and tissue catecholamines in normal and spontaneously hypertensive rats (SHR). MFMD 10 mg·kg⁻¹ (i.p.) effectively antagonizes thel-DOPA induced increase in heart dopamine (DA). This action is also seen after 15 or 50 mg·kg⁻¹. The accumulation of DA in the brain is very much reduced by MFMD 50 mg ·kg⁻¹ while after 15 or, especially, 10 mg·kg⁻¹ more DA is formed in the rrain than afterl-DOPA alone, probably due to the peripheral decarboxylase inhibition which presents morel-DOPA to the brain. We conclude that MFMD 10 mg ·kg⁻¹ gives a relatively selective peripheral inhibition of the decarboxylation ofl-DOPA and this dose combination was accordingly found to result in a reduction of blood pressure in conscious animals. This hypotensive response tol-DOPA was attenuated after MFMD 15 mg·kg⁻¹ and was absent after MFMD 50 mg·kg⁻¹. Interestingly, the hypotensive effect ofl-DOPA after MFMD 10 or 15 mg·kg⁻¹ was more pronounced in SHR.