Effects Of D2 Receptor Agonists Research Articles

Obesity, dopamine and the metabolic syndrome: potential of dopaminergic agents in the control of metabolism

Purpose of review To discuss and gather together current knowledge pertaining to the role of dopaminergic neurotransmission in the control of various metabolic and behavioural processes that are often disrupted in obese humans, and to highlight evidence that dopaminergic drugs can ameliorate various metabolic anomalies associated with obesity. Recent findings Dopamine is involved in the control of food intake, energy expenditure, glucose and lipid metabolism, blood pressure and insulin release. Dopaminergic (D2 receptor) neurotransmission is diminished in the brains of obese animal models and humans. D2 receptor activation facilitates glucose metabolism, lowers blood pressure and stimulates resting energy expenditure in non-diabetic obese individuals. Long-term treatment with D2 receptor agonists improves metabolic control in obese humans with type 2 diabetes. Summary The (re)activation of diminished D2 receptor-mediated neurotransmission simultaneously ameliorates a number of metabolic anomalies associated with obesity in humans. D2 receptor agonistic drugs could be an asset to our armamentarium in the battle against type 2 diabetes and cardiovascular disease. Their clinical efficacy may, however, be curtailed by the fact that D2 receptors are less abundant in obesity. The (patho-)biology of dopaminergic neurotransmission in obese individuals thus requires further study to be able to design drugs that can boost the beneficial effects of D2 receptor agonists in obese humans.

Effects of dopamine D1 ligands on eye blinking in monkeys: efficacy, antagonism, and D1/D2 interactions.

Dopamine D1 ligands have been classified and ordered according to efficacy in both in vitro and in vivo studies. In the present experiments, dopamine D1 ligands reported to differ in in vitro efficacy were evaluated for efficacy-related effects on eye blinking in squirrel monkeys. Additional comparisons were made with the effects of D2 receptor agonists and indirect dopamine agonists. The results show that D1 agonists increased eye blinking in an efficacy-related manner, whereas the D1 receptor blocker SCH 39166 [(-)-trans-6,7,7alpha,8,9,13beta-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naphtho[2,1-b]azepine] only decreased rates of eye blinking. D1 high-efficacy agonists induced rates of eye blinking that were 2- to 3-fold greater than observed with dopamine D2 agonists and indirect agonists. In drug combination experiments, increases in eye blinking induced by the D1 high-efficacy agonist R-(+)-6-Br-APB [R-(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] were antagonized by both the D1 antagonist SCH 39166 and the lower efficacy agonist SKF 83959 [6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide], consistent with dopamine D1 receptor mediation of these behavioral effects. The dopamine D2 agonist (+)-PHNO [(+)-N-propyl-hydroxynaphthoxazine], which selectively activates dopamine D2 receptors, also attenuated D1 agonist-induced increase in eye blinking, suggesting that D2 receptor actions may inhibit D1-mediated increases in eye blinking. Overall, eye blink rate appears to be a robust behavioral measure that can be used to measure changes in dopaminergic D1 signaling and as a functional assay of agonist efficacy at dopamine D1 receptors.

SLV310, a molecule combining potent dopamine D 2 receptor antagonism with serotonin reuptake inhibition: In vitro and in vivo neurochemistry

The interaction between muscarinic-cholinergic and dopaminergic systems in the modulation of memory storage of Y-maze discrimination (YMD) task was examined in C57BL/6 and DBA/2 strains of mice. In C57BL/6 mice, post-training systemic (i.p.) administration of the D2-agonist quinpirole facilitated retention and the D2-antagonist (−)-sulpiride impaired retention. Opposite effects were observed in DBA/2 strain. The facilitating or impairing effects of quinpirole and (−)-sulpiride were blocked by simultaneous post-training administration of muscarinic-cholinergic agonists and antagonists. The memory enhancing effects of the cholinergic agonist oxotremorine were not blocked by simultaneous administration of sulpiride in C57BL/6 mice or quinpirole in DBA/2 mice. Furthermore, the memory impairing effects of the cholinergic antagonist atropine were not blocked by simultaneous administration of quinpirole in C57BL/6 mice or sulpiride in DBA/2 mice. These findings indicate that the effects of D2-receptor agonists and antagonists on retention of YMD task are strain-dependent and mediated through muscarinic-cholinergic mechanisms.