Alpha-Monofluoromethyldopa (MFMD) in combination with L-DOPA Effects on tissue catecholamines and blood pressure in rats.
We have investigated the interaction of alpha-monofluoromethyldopa (MFMD) with the effects of i.p. injected L-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 the L-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 brain than after L-DOPA alone, probably due to the peripheral decarboxylase inhibition which presents more L-DOPA to the brain. We conclude that MFMD 10 mg.kg-1 gives a relatively selective peripheral inhibition of the decarboxylation of L-DOPA and this dose combination was accordingly found to result in a reduction of blood pressure in conscious animals. This hypotensive response to L-DOPA was attenuated after MFMD 15 mg.kg-1 and was absent after MFMD 50 mg.kg-1. Interestingly, the hypotensive effect of L-DOPA after MFMD 10 or 15 mg.kg-1 was more pronounced in SHR.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism*; D004347:Drug Interactions; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008750:Methyldopa / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology
D002395:Catecholamines; D012965:Sodium Chloride; D007980:Levodopa; D008750:Methyldopa; C019494:alpha-monofluoromethyldopa