PT  - JOURNAL ARTICLE
AU  - Y Claustre
AU  - D Fage
AU  - B Zivkovic
AU  - B Scatton
TI  - Relative selectivity of 6,7-dihydroxy-2-dimethylaminotetralin, N-n-propyl-3-(3-hydroxyphenyl)piperidine, N-n-propylnorapomorphine and pergolide as agonists at striatal dopamine autoreceptors and postsynaptic dopamine receptors.
DP  - 1985 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 519--525
VI  - 232
IP  - 2
4099  - http://jpet.aspetjournals.org/content/232/2/519.short
4100  - http://jpet.aspetjournals.org/content/232/2/519.full
SO  - J Pharmacol Exp Ther1985 Feb 01; 232
AB  - 6,7-Dihydroxy-2-dimethylaminotetralin (TL-99), N-n-propyl-3-(3-hydroxyphenylpiperidine [(+/-)-3-PPP], N-n-propylnorapomorphine and pergolide were evaluated for activity on a number of biochemical parameters that are presumed to indicate an agonist effect at dopamine (DA) autoreceptors (antagonism of the gamma-hydroxybutyrate-induced increase in dopa formation), at postsynaptic DA receptors (elevation of acetylcholine levels) or at both types of DA receptors (diminution of DA synthesis and homovanillic acid levels) in rat striatum. All four agents decreased striatal dopa accumulation (in the presence and in the absence of gamma-hydroxybutyrate). N-propylnorapomorphine, pergolide and TL-99 also reduced homovanillic acid levels and increased acetylcholine concentrations in striatum whereas (+/-)-3-PPP was inactive. The compounds were all more potent in diminishing dopa accumulation caused by gamma-hydroxybutyrate treatment than in increasing acetylcholine levels [(+/-)-3-PPP showing the highest dissociation] indicating a preferential agonist activity at DA autoreceptors. The relative selectivity of the compounds for DA autoreceptors and postsynaptic DA receptors was evaluated further by studying the antagonism by these drugs of the activation of striatal dopa formation (index of both DA autoreceptor and postsynaptic DA receptor stimulation) and tyrosine hydroxylase (index of postsynaptic DA receptor stimulation only) induced by haloperidol or reserpine. The DA agonists were all more potent in antagonizing the neuroleptic-induced increase in DA synthesis than in counteracting the drug-induced activation of tyrosine hydroxylase, with (+/-)-3PPP exhibiting the highest dissociation. The present results indicate that the DA agonists studied possess some selectivity for striatal DA autoreceptors, (+/-)-3-PPP being the most selective in this respect.