Dopamine D2-receptor

Fig. 2. Molecular modeling of dopamine D2 receptor agonists used to define the molecular conformation needed for selective high affinity binding.

Correlation between clinical effectiveness and receptor affinities, however, can be seen with other receptors in addition to the dopamine D2 receptor. These include other dopaminergic receptors, as well as noradrenergic and serotonergic receptors. For example, most antipsychotics also have high affinity for a -adrenoceptors and 5-HT2 receptors (225). Some antipsychotics have been shown to be selective for the adrenoceptor versus the a -adrenoceptor, for example, spiperone [749-02-0] (226) and risperidone (61) (221]... 

Kapur S, Seeman P (2001) Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics A new hypothesis. Am J Psychiatry 158 360-369... 

Dopamine D2 receptors are involved in some emetic responses but studies have also suggested that activation of D3 receptors in the area postrema may either produce vomiting or enhance that elicited by D2 receptor activation. 

Parkinsonian patients receiving the dopamine precursor, levodopa or dopamine receptor agonists, such as bromocriptine and apomoiphine may experience nausea and vomiting due to stimulation of dopamine D2 receptors in the CTZ. 

Neuroleptics or antipsychotics suppress the positive symptoms of schizophrenia such as combativeness, hallucinations and formal thought disorder. Some also alleviate the negative symptoms such as affective blunting, withdrawal and seclusiveness. Neuroleptics also produce a state of apathy and emotional indifference. Most neuroleptics block dopamine D2-receptors but some, like clozapine, also block dopamine D4-receptors or serotonin 5-hydroxytryptamine2A-receptors. 

Prolactin is peptide hormone secreted by the pituitary gland. It acts on prolactin receptors in breast tissue where it stimulates production of casein and lactalbu-min. It also acts on the testes and ovaries to inhibit the effects of gonadotrophins. Since the secretion of prolactin is under tonic dopaminergic inhibition by the hypothalamus, dopamine D2-receptor antagonists... 

Derivatives of (S) N-[(l-ethyl-2-pyrrohdinyl)methyl]-6-methoxy benzamide 3 are dopamine D2 receptor antagonists. Samanta et al. obtained the following MLR QSAR for 49 derivatives with the general structure 3 [30] ... 

Samanta, S., Debnath, B., Gayen, S., Ghosh, B Basu, A., Srikanth, K., Jha, T. QSAR modeling on dopamine D2 receptor binding affinity of 5-methoxy benzamides. Farmaco 2005, 60, 818-825. 

In the following example from the literature [39], the correlahon with lipophilicity is studied for 47 compounds in two series which have been designed for dopamine D2 receptor affinity. As seen in Fig. 17.1, there is no clear relahon between D2 activity and lipophilicity (r=0.11). 

Diaminopyrimidines, 19 (1982) 269 Digitalis recognition matrix, 30 (1993) 135 Diuretic drugs, 1 (1961) 132 DNA-binding drugs, 16 (1979) 151 Dopamine D2 receptor agonists,... 

The CTZ, located outside the blood-brain barrier (BBB), is exposed to cerebrospinal fluid and blood.2,3 Therefore it is easily stimulated by uremia, acidosis, and the circulation of toxins such as chemotherapeutic agents. The CTZ has many serotonin type 3 (5-HT3), neurokinin-1 (NKj), and dopamine (D2) receptors.2 Visceral vagal nerve fibers are rich in 5-HT3 receptors. They respond to gastrointestinal distention, mucosal irritation, and infection. 

Stimulation of dopamine (D2) receptors in the CTZ leads to nausea and vomiting (Fig. 17-1). Phenothiazine antiemetics... 

While FGAs exert most of their effect through dopamine receptor blockade at the dopamine (D2) receptor, the SGAs... 

Xing, Q. el al. (2006a). The relationship between the therapeutic response to risperidone and the dopamine D2 receptor polymorphism in Chinese schizophrenia patients. Int. J. Neuropsy-chopharmacol., 10, 631-7. 

Allosteric interactions on GPCRs have been observed for the muscarinic [11-13], adenosine Ai [14], a2A-adrenergic [15-17], and dopamine D2 receptor [18]. This chapter focuses only on two allosteric phenomena, as well as their potential for therapeutic exploitation that on the muscarinic receptor and that on the adenosine receptor. 

Bagetta G., Sarro G. D., Priolo E., Nistico G. (1988). Ventral tegmental area site through which dopamine D2-receptor agonists evoke behavioral and electrocortical sleep in rats. Br. J. Pharmacol 95, 860-6. 

Brock J. W., Hamdi A., Ross K., Payne S., Prasad C. (1995). REM sleep deprivation alters dopamine D2 receptor binding in the rat frontal cortex. Pharmacol. 

Ennis M., Zhou F., Ciombor K. et al. (2001). Dopamine D2 receptor-mediated presynaptic inhibition of olfactory nerve terminals. J. Neurophysiol. 86,... 

Ferre, S., von Euler, G., Johansson, B., Fredholm, B. B. Fuxe, K. (1991). Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Proc. Natl Acad. Sci. USA 88 (16), 7238-41. 

Anokhin, A.P., Torodov, A.A., Madden, P.A.F., Grant, J.D., Heath, A.C. Brain event-related potentials, dopamine D2 receptor gene polymorphism, and smoking. Genet. Epidemiol. 17(Suppl. 1) S37, 1999. 

Wang, G.J., Volkow, N.D., Fowler, J.S. et al. Dopamine D2 receptor availability in opiate-dependent subjects before and after naloxone-precipitated withdrawal. Neuropsychopharmacology. 16 174, 1997. 

SpyrakiC., SealfonS. Regulation of dopamine D2 receptor mRNA expression in the olfactory tubercle by cocaine. Mol. Brain Res. 19 313, 1993. 

DBH, dopamine / -hydroxylase DRD2, dopamine D2 receptor DRD4, dopamine D4 receptor CYP2A6, cytochrome P450 2A6 CYP2D6, cytochrome P450 2D6. 

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