title: A comparison of the potencies of various dopamine receptor agonists in models for pre- and postsynaptic receptor activity.
abstract: Several dopamine (DA) receptor agonists, notably N,N-dipropyl-2-aminotetralin analogues differing in the number and position of phenolic hydroxyl groups, were evaluated in model systems for pre- and postsynaptic dopaminergic activity. Apomorphine, piribedil and pergolide were included for comparison. All compounds inhibited the gamma-butyrolactone (GBL)-induced increase in DA concentrations in the rat striatum and olfactory tubercle, although a dose-dependency could not be demonstrated for one of the compounds, i.e. N,N-dipropyl-2-amino-5,6-dihydroxy-tetralin. In addition to the reversal of the DA-increase all compounds decreased the HVA and DOPAC levels in a dose-dependent manner, in much the same way as in normal, non GBL-pretreated rats. The potencies of the drugs to decrease HVA in normal rats and to inhibit the DA-increase and to decrease HVA in GBL-pretreated rats, both in the striatum and the olfactory tubercle were compared with each other and with the potencies to induce stereotyped behaviour. It may be concluded that (1) N,N-dipropyl-2-amino-7-hydroxytetralin shows the largest difference in activity in the biochemical and the behavioural models, suggesting a selective presynaptic activity. This was corroborated by the appearance of a marked hypomotility after low doses of this compound; (2) The potencies to decrease striatal HVA concentrations are generally somewhat different from the potencies to inhibit GBL-induced DA-increases, but appear to be comparable to the potencies to inhibit GBL-induced dihydroxyphenylalanine (DOPA)-increases; (3) There is no indication that the DA agonists in general are more potent at presynaptic receptors in the tubercle than in the striatum.
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D006719:Homovanillic Acid / Q000032:analysis; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects; D010479:Pergolide; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
chemical_list: D004873:Ergolines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D010479:Pergolide; D001971:Bromocriptine; D015107:4-Butyrolactone; D004298:Dopamine; D006719:Homovanillic Acid