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.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002415:Cats; D002421:Caudate Nucleus / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D006426:Hemicholinium 3 / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011954:Receptors, Dopamine / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013469:Sulpiride / Q000494:pharmacology; D014316:Tritium
D011954:Receptors, Dopamine; D014316:Tritium; D006426:Hemicholinium 3; D013469:Sulpiride; D001058:Apomorphine; D000109:Acetylcholine; D004298:Dopamine