Summary
The agonistic and antagonistic effects of the new compound SCH 23390 were tested in functional model systems for the D-1 dopamine receptor and for the D-2 dopamine receptor in vitro. In superfused rat neostriatal slices the increase in the efflux of cyclic AMP was used as a parameter for D-1 receptor stimulation. D-2 receptor stimulation was measured as the decrease in the K+-evoked release of [3H]-acetylcholine. SCH 23390 had no agonistic activity in these two models. SCH 23390 was a potent antagonist of the stimulating effect of dopamine in the D-1 receptor model (apparent pA2=7.28). SCH 23390 also antagonized the effect of the D-2 receptor agonist LY 141865 in the D-2 receptor model (apparent pA2=6.34). This D-2 receptor antagonism proved to be of a competitive nature.
This is a preview of subscription content, log in via an institution to check access.
References
Brooker G, Harper JF, Terasaki WL, Moylan RD (1979) Radioimmunoassay of cyclic AMP and cyclic GMP. Adv Cycl Nucl Res 10:1–33
Hyttel J (1983) SCH 23390 — The first selective dopamine D-1 antagonist. European J Pharmacol 91:153–154
Iorio LC, Barnett A, Leitz FH, Houser VP, Korduba CA (1983) SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems. J Pharmacol Exp Ther 226:462–468
Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96
Lehmann J, Langer SZ (1983) The striatal cholinergic interneurons: synaptic target of dopaminergic terminals? Neuroscience 10:1105–1119
Scatton B (1982) Further evidence for the involvement of D2, but not D1 dopamine receptors in dopaminergic control of striatal cholinergic transmission. Life Sci 31:2883–2890
Starke K, Späth L, Lang JD, Adelung C (1983) Further functional in vitro comparison of pre- and postsynaptic dopamine receptors in the rabbit caudate nucleus. Naunyn-Schmiedeberg's Arch Pharmacol 323:298–306
Stoof JC, Kebabian JW (1981) Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum. Nature 294:366–368
Stoof JC, Kebabian JW (1982) Independent in vitro regulation by the D-2 dopamine receptor of dopamine-stimulated efflux of cyclic AMP and K+-stimulated release of acetylcholine from rat neostriatum. Brain Res 250:263–270
Tsuruta K, Frey EA, Grewe CW, Cote TE, Eskay RL, Kebabian JW (1981) Evidence that LY-141865 specifically stimulates the D-2 dopamine receptor. Nature 292:463–465
Watling KJ, Dowling JE (1981) Dopaminergic mechanisms in the teleost retina. I. Dopamine-sensitive adenylate cyclase in homogenates of carp retina; effects of agonists, antagonists and ergots. J Neurochem 36:559–569
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Plantjé, J.F., Daus, F.J., Hansen, H.A. et al. SCH 23390 blocks D-1 and D-2 dopamine receptors in rat neostriatum in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 327, 180–182 (1984). https://doi.org/10.1007/BF00500914
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00500914