(+)-AJ 76 and (+)-UH 232: central stimulants acting as preferential dopamine autoreceptor antagonists
Svensson K, Johansson AM,
Magnusson T, Carlsson A
Naunyn Schmiedebergs Arch Pharmacol 1986 Nov; 334(3):234-45


The biochemical and behavioral effects of the putative dopamine autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76 and cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, were evaluated in various in vivo models in rats. Both compounds produced a marked elevation in brain dopamine synthesis and turnover with only slight effects on the synthesis and turnover of serotonin (5-HT) and noradrenaline being noted. (+)-AJ 76 and (+)-UH 232 also failed to antagonize the decrease in cortical noradrenaline synthesis rate caused by the alpha 2 agonist clonidine. The apomorphine-induced decrease in dopamine synthesis rate in gamma-butyrolactone (GBL) treated animals was completely blocked by (+)-AJ 76 and (+)-UH 232 but not by d-amphetamine or methylphenidate. In activity experiments using habituated animals, (+)-AJ 76 and (+)-UH 232 produced locomotor stimulation and weak stereotypies and antagonized the sedative effects of low doses of apomorphine. Locomotor hyperactivity induced by apomorphine or the dopamine agonist DiPr-5,6-ADTN was antagonized by (+)-UH 232 and to a lesser degree by (+)-AJ 76. The locomotor hyperactivity produced by (+)-AJ 76, (+)-UH 232 and methylphenidate was completely prevented by reserpine pretreatment and partially blocked by the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MT), whereas d-amphetamine-induced hyperactivity was only antagonized by alpha-MT pretreatment. It is concluded that (+)-AJ 76 and (+)-UH 232 produce behavioral stimulation via a preferential antagonism on central dopamine autoreceptors, an action different from that of all known stimulants including apomorphine, d-amphetamine and methylphenidate. (+)-AJ 76 and (+)-UH 232 possess but weak antagonistic effects on postsynaptic dopamine receptors and only the latter compound is able to induce sedation in rats.

AJ 76
Cocaine hotspots
AJ 76 and UH 232
Dopaminergic flies?
Dopaminergic agents
The coke-craving brain
Monoamines, cocaine and rats
Freebasing flies go hyperkinetic
AJ 76, UH 232 and dopamine release
GBR12909: a dopaminergic antidepressant?

01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24

BLTC Research
Wirehead Hedonism
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best to Take Crack Cocaine?

swan image
The Good Drug Guide
The Responsible Parent's Guide To
Healthy Mood Boosters For All The Family