The central effects of a novel dopamine agonist

doi:10.1016/0014-2999(78)90148-6

European Journal of Pharmacology

Volume 50, Issue 4, 15 August 1978, Pages 419-430

https://doi.org/10.1016/0014-2999(78)90148-6 Get rights and content

Abstract

A new peripheral dopamine agonist which causes dopaminergic renal vasolidation, was tested for central dopaminergic activity. SK & F 38393 stimulated the dopamine-sensitive adenylate cyclase in homogenates of rat caudate, as a partial agonist, and caused contralateral rotation in rats with unilateral 6-OHDA lesions of substantia nigra. Rotation was shown to be due to a direct effect on supersensitive dopamine receptors. Stimulation of cAMP formation and rotation were blocked by dopamine antagonists. In contrast to other dopamine agonists, SK & F 38393 did not cause stereotypy, emesis or inhibition of prolactin release, nor did SK & F 38393 affect dopamine turnover. The results suggest that SK & F 38393 may selectively stimulate supersensitive central dopamine receptors in vivo or may activate only a certain subclass of dopamine receptors including the receptor in the renal vasculature and the adenylate cyclase coupled postsynaptic receptor in the caudate.

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There are two mechanistic issues that are relevant for future study. The first selective D1 agonist SKF38393 had low intrinsic activity (Setler et al., 1978), possibly explaining why it failed in both MPTP-NHP and human trials (Boyce et al., 1990; Close et al., 1985). Dihydrexidine and many later compounds had full or high efficacy (Kebabian et al., 1992; Lovenberg et al., 1989; Michaelides et al., 1995; Shiosaki et al., 1996) and were effective antiparkinson agents.
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The central effects of a novel dopamine agonist

Abstract

Life Sci.

Neuropharmacology

European J. Pharmacol.

Brain Res.

European J. Pharmacol.

Life Sci.

European J. Pharmacol.

Gastroenterology

Brain Res.

Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines

J. Pharmacol. Exptl. Therap.

Dopamine-sensitive adenylyl cyclase in human caudate nucleus

Arch. Gen. Psychiat.

Dopamine-sensitive adenylate cyclase in mammalian brain: A possible site of action of antipsychotic drugs

Effect of ergot drugs on central catecholamine neurons: evidence for a stimulation of central dopamine neurons

J. Pharm. Pharmacol.

Dopamine-like renal and mesenteric vasodilation caused by apomorphine, 6-propyl norapomorphine and 2-amino-6,7-dihydroxyl-1,2,3,4-tetrahydronaphthalene

Nature

The rat forebrain in stereotaxic coordinates

Trans. Royal Neth. Acad. Sci.