Ergot alkaloids: interaction with presynaptic dopamine receptors in the neostriatum and olfactory tubercles.
Several ergot alkaloids, bromocriptine, ergocornine and lergotrile were shown to have potent agonist action at presynaptic dopamine receptors on striatal and mesolimbic nerve terminals in an in vivo model system. These agents blocked the increase in accumulation of striatal dihydroxyphenylalanine produced when impulse flow in the nigro-striatal dopamine system was inhibited by administration of gamma-butyrolactone. Administration of dopamine receptor blockers such as haloperidol prior to administration of the ergot alkaloids and apomorphine prevented the inhibitory effects of these agonists. However, when haloperidol was administered 50 min after the agonists although it completely blocked the effects of apomorphine it only partially antagonized the inhibitory effects of ergocornine and lergotrile and was ineffective in reversing the inhibitory effects of bromocriptine. Thus, this study in contrast to in vitro studies indicates that the ergot alkaloids do have potent effects on presynaptic dopamine nerve terminal receptors and that these agents, especially bromocriptine may interact non-competitively or irreversibly with presynaptic dopamine receptors.
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004876:Ergot Alkaloids / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology; D009830:Olfactory Bulb / Q000187:drug effects*; D011699:Putamen / Q000187:drug effects*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*
D004876:Ergot Alkaloids; D011954:Receptors, Dopamine; D004295:Dihydroxyphenylalanine; D006220:Haloperidol; D015107:4-Butyrolactone