Disease relevance of (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol

• These results show a lesser liability of A-86929 and A-77636 to reproduce dyskinesia in L-dopa-primed MPTP-lesioned subjects while maintaining effective antiparkinsonian activity and producing a more naturalistic motor response [1].
• Upon reintroduction of L-dopa concurrently with continued A-77636 administration, dystonic, but virtually no choreic dyskinesias appeared and behaviour was once again free of stereotypy and hyperkinesis, contrasting dramatically with the presence of these behaviours along with abundant chorea when L-dopa is given alone [1].
• In the present study, we show that the selective D1 agonist A77636 also induces orofacial dyskinesia when injected into the subthalamic nucleus of awake rats, thus confirming a role for D1 receptors in this effect [2].

Psychiatry related information on (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol

• RESULTS: A77636 (1.0 and 2.5 mg/kg, i.p.) produced a greater threshold-lowering effect in food-restricted than ad libitum fed rats but produced variable effects on locomotor activity with no difference between groups [3].

High impact information on (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol

• Both the selective D1-like agonist, A-77636, and the D2-like agonist, quinpirole, also induced Fos in orexin cells, suggesting that stimulation of either receptor subtype is sufficient to activate orexin neurons [4].
• Comparison of interactions of D1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents [5].
• Because A-77636 consistently attenuated the present effects of cocaine, it may prove more useful than the others as a pharmacotherapy to treat cocaine abuse [5].
• After a week of twice-daily L-dopa dosing, administration of the long-acting D1 agonist A-77636 initially dramatically enhanced locomotion and reproduced dyskinesia with prominent dystonia, but after repeated administration of A-77636, dyskinesia and in particular chorea, gradually disappeared [1].
• Preincubation of rat striatal membranes with A-77636 resulted in a large decrease in D1 receptor binding, despite repeated washings, whereas A-81686 pretreatment caused only a small reduction in D1 receptor binding [6].

Chemical compound and disease context of (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol

• When tested in marmosets treated with MPTP to induce a parkinsonian-like state, A-77636 increases locomotor activity and decreases the severity of the parkinsonian-like symptoms: the compound is active after either subcutaneous or oral administration [7].

Biological context of (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol

• All three compounds dose-dependently increased the number of penile erections, with the full agonist A77636 showing a more pronounced effect with respect to the other two [8].
• The results indicate that A-77636 exerted a suppressant effect on food intake, due principally to a reduction in meal size and duration [9].

Anatomical context of (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol

• Higher doses of A-77636 produce forelimb clonus in rats and mice [7].
• Systemic injections of the selective, full, D1 agonists A-77636 and SKF-82958 induced pronounced Fos-like immunoreactivity in the islands of Calleja in the olfactory tubercle of intact rats [10].

Associations of (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol with other chemical compounds

• Treatment of intact rats with the full D(1) dopamine agonist A-77636 induced Fos-like immunoreactivity in the medial and, to a lesser extent, the lateral portions of the striatum [11].

Gene context of (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol

• We now explore the effects of acute versus repeated administration of A-77636 and the relative roles of D-1 and D-2 receptor involvement in its antiparkinsonian actions [12].

Analytical, diagnostic and therapeutic context of (1R)-3-(1-adamantyl)-1-(aminomethyl)isochroman-5,6-diol

• Central treatments consisted of microinjections of quinpirole (0.3-10.0 micrograms/0.5 microliter) directly into the caudal NAcc, CP or cortex or A-77636 (30 micrograms/0.5 microliter) into the caudal NAcc or CP [13].

References