Novel Dopamine Agonists of the Indolylbutylamine Type: Pre- Versus Postsynaptic Activity in Various in vivo and in vitro Models
Recently, we demonstrated dopaminergic activity in a novel structural class of coapounds, the indole-alkyl-piperidines (Seyfried et al. 1982, Hausberg et al. 1983) which are structurally unrelated to either rigid dopamine analogues or to ergot type compounds. We now report actions on pre- and postsynaptic dopamine receptors of one potent representative of this series, i.e. EMD 38 362 (5-hydroxy-3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-(1))-butyl-(1))-indole, hydrochloride). Amongst others, we used several models considered to be highly specific for the pharmacological site of action, viz., dopa accumulation under conditions of inhibited impulse flow for presynaptic activity and changes in acetylcholine levels and release, reflecting actions on the dopamino-receptive, postsynaptic cholinergic interneurons.
KeywordsDopamine Hydrochloride Choline Acetylcholine Acetyl
- Hausberg, H.-H., Boettcher, H., Fuchs, A., Gottschlich, R., Koppe, V., Minck, K.-O., Poetsch, E., Saiko, O. and Seyfried, C.A. (1983). Indole-alkyl-piperidines, a new class of dopamine agonists. Acta Pharm. Suecica, Suppl. 2, 213–217.Google Scholar
- Seyfried, C.A., Fuxe, K., Wolf, H.-P. and Agnati, L.F. (1982). Demonstration of a new type of dopamine receptor agonist: an indolyl-3-butylamine. Actions at intact versus supersensitive dopamine receptors in the rat forebrain. Acta Physiol. Scand. 116, 465–468.Google Scholar