Cardiovascular effects of dopamine and some methylated and fluorinated derivatives in pithed normotensive rats.

The cardiovascular effects of dopamine, (R)-alpha-methyldopamine, (S)-alpha-methyldopamine, (R)-alpha-fluoromethyldopamine, (R,S)-alpha-difluoromethyldopamine and (R)-alpha-fluoromethyltyramine were characterized in the pithed normotensive rat. The activity on alpha 1-adrenoceptors in the resistance vessels of the pithed rat was identified by prazosin antagonism, on alpha 2-adrenoceptors by rauwolscine antagonism, on beta 1-adrenoceptors by chronotropic effects sensitive to atenolol antagonism and on vascular beta 2-adrenoceptors by potentiation of pressor responses by ICI 118,551. Indirect sympathomimetic effects were studied by reserpine pretreatment and the influence of neuronal uptake by the effect of cocaine on the chronotropic effects of the agents. The alpha-methyl substitution induces pronounced beta 2-agonistic properties especially for the (S)-enantiomer, which also displays some selectivity for alpha 2-adrenoceptors. This selectivity is diminished by the substitution of one fluorine atom in the methyl group. The introduction of two fluorine atoms leads to a reduction in potency on all adrenoceptors studied.