Detail of "85798-08-9"

Reference

SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons

SCH-23390 antagonism of a D-2 dopamine agonist depends upon catecholaminergic neurons. Breese, George R.; Mueller, Robert A. (Sch. Med., UNC, Chapel Hill, NC 27514, USA). Eur. J. Pharmacol., 113(1), 109-14 (English) 1985. CODEN: EJPHAZ. ISSN: 0014-2999. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 SCH-23390 [87134-87-0], a selective D-1 dopamine antagonist, antagonized the locomotor stimulation induced by the D-2 agonist LY-171555 [85798-08-9], an action similar to that for haloperidol in control animals. However, this action of SCH-23390 was prevented in rats treated with 6-hydroxydopamine (6-OHDA) or with reserpine plus a-methyltyrosine pretreatment. Thus, the action of SCH-23390 to antagonize D-2 dopamine receptor actions is dependent upon functional catecholamine-contg. neurons. In contrast to the lack of action of SCH-23390 to antagonize LY-171555 in 6-OHDA-treated rats, SCH-23390 blocked the locomotor stimulation induced by SKF-38393 [67287-49-4], a D-1 dopamine agonist, after this treatment. Thus, D-1 dopamine receptors are distinct from D-2 receptor sites and can exhibit a behavior similar to that obsd. when D-2 receptors are stimulated. The D-1 receptor sites may modulate D-2 dopamine receptor function through a mechanism dependent upon functionally intact catecholamine-contg. neurons.

Dopamine agonist-induced locomotor activity in rats treated with 6-hydroxydopamine at differing ages: functional supersensitivity of D-1 dopamine receptors in neonatally lesioned rats

Dopamine agonist-induced locomotor activity in rats treated with 6-hydroxydopamine at differing ages: functional supersensitivity of D-1 dopamine receptors in neonatally lesioned rats. Breese, George R.; Napier, T. Celeste; Mueller, Robert A. (Sch. Med., Univ. North Carolina, Chapel Hill, NC 27514, USA). J. Pharmacol. Exp. Ther., 234(2), 447-55 (English) 1985. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 Locomotor responses caused by dopamine receptor agonists with presumed specificity for D-1 or D-2 receptor subtypes were compared to apomorphine-induced locomotion in neonatally and adult 6-hydroxydopamine (6-OHDA)-treated rats. In adult 6-OHDA-treated rats, apomorphine and the D-2 agonist LY-171555 [85798-08-9] produced a marked, dose-related increase in locomotor activity. Increases in locomotion obsd. in neonatally 6-OHDA-treated rats after apomorphine and LY-171555 administration were less than one-third of those seen in rats treated as adults with 6-OHDA. Neonatally 6-OHDA-treated rats, pos. for L-dihydroxyphenylalanine-induced self-biting, exhibited a small increase in locomotion after a single exposure to SKF-3839 [67287-49-4], a D-1 dopamine agonist. Subsequent administration of SKF-38393 to these rats resulted in an addnl. elevation of the locomotor response which reached a max. after four doses. Adult 6-OHDA-treated rats were less sensitive to the locomotor-stimulant effects of SKF-38393 than were neonatally 6-OHDA-treated rats. SKF-38393 and LY-171555 produced several behaviors in neonatally 6-OHDA-treated rats that were similar. These results indicate that D-1 dopamine receptors contribute to modulation of central dopaminergic function. Haloperidol and cis-flupentixol antagonized apomorphine-induced locomotion comparably in control and adult 6-OHDA-treated rats. The D-1 dopamine receptor antagonist SCH-23390 was a less effective blocker of apomorphine-induced locomotion in 6-OHDA-treated rats than in controls. Therefore, the ability of SCH-23390 to attenuate apomorphine in control rats is likely dependent upon intact catecholamine-contg. neurons. Haloperidol and cis-flupentixol antagonized LY-171555-induced locomotion in adult 6-OHDA-treated rats, but SCH-23390 did not. However, SCH 23390 completely antagonized the locomotion induced by SKF-38393 in adult and neonatally 6-OHDA-treated rats. Thus, LY-171555 and SKF-38393 appear to act on sep., distinct sites to increase locomotion. These data suggest a primary increase in the functional sensitivity of D-1 dopamine receptors responsible for locomotor activity in neonatally 6-OHDA-treated rats, with only a minor increase in D-2 receptor sensitivity. Adult 6-OHDA-treated rats demonstrate a functional increase in D-2 dopamine receptor sensitivity with some D-1 receptor supersensitivity. Therefore, it is possible that selective changes in D-1 and D-2 dopamine receptors may be assocd. with clin. syndromes with central dopamine deficiencies, and selective manipulation of these receptors may offer new avenues of therapy for such central dysfunctions.