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... 

The antipsychotic activity of neuroleptics (D2-like receptor antagonists) has led to the development of many different ligands for the D2 receptor. These drugs... 

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... 

Despite this profusion of receptors the Di and D2 predominate (over 90% of total) and most known effects of DA, its agonists and antagonists are mediated through the D2 receptor. Although the above nomenclature is now accepted it might have been better, as suggested by Sibley and Monsma (1992), to retain Di and D2 to represent the two families and then subdivide them as Dja for (Di), Dib for (D5), then D2A for (D2), D2B for (D3) and D2C for (D4), even though variants of all five have been found. Their... 

Figure 7.4 Comparative schematic representation of the Dj ( ) and D (—) dopamine receptor. The figure attempts to highlight the major differences between extra- and intracellular loops, especially the intracellular loops between transmembrane sections 5 and 6 and the much longer C terminal of the Dj compared with the D2 receptor. It is based on the proposed topography of Sibley and Monsma (1992). The thickened length of the D2 receptor represents the amino-acid sequence missing in the short form of the receptor. No attempt has been made to show differences in amino-acid sequencing or transmembrane topography...

S = short, L = long versions of D2 receptor, f = main effect observed, ( ) = some evidence of an effect. See Sibley and Monsma (1997), Sokoloff and Schwartz (1995) and Strange (1996). 

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