Stereoisomers of apomorphine differ in affinity and intrinsic activity at presynaptic dopamine receptors modulating [3H]dopamine and [3H]acetylcholine release in slices of cat caudate.

We investigated the effects of R(-)-apomorphine and S(+)-apomorphine on dopamine receptors modulating electrically evoked [3H]dopamine and [3H]acetylcholine release from slices of cat caudate nucleus. R(-)-Apomorphine inhibited the release of both [3H]dopamine and [3H]acetylcholine with an IC50 of 20 nM, while S(+)-apomorphine was without inhibitory action on the electrically evoked release of either neurotransmitter at concentrations up to 1 microM. At a concentration of 1 microM, however, S(+)-apomorphine antagonized the inhibition by R(-)-apomorphine, producing a parallel five-fold shift to the right in the concentration-response curve to R(-)-apomorphine. These results indicate that S(+)-apomorphine is devoid of intrinsic activity to stimulate presynaptic dopamine receptors modulating the electrically evoked release of dopamine and acetylcholine. In addition, S(+)-apomorphine has an approximately ten-fold lower affinity for presynaptic dopamine receptors compared to R(-)-apomorphine.