Dopamine D2 receptors and dopamine metabolism. Relationship between biochemical and behavioural effects of substituted benzamide drugs.
The effect of the substituted benzamide dopamine D2 receptor antagonists sulpiride, raclopride, FLA 966(-), FLA 988(-), eticlopride and remoxipride as well as the "classical" dopamine antagonists, haloperidol and chlorpromazine, on the concentrations of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain of the rat was investigated. All compounds increased the turnover of dopamine, as defined by increased concentrations of DOPAC and HVA (without change in the concentration of dopamine) in the striatum in a dose-dependent manner. The doses of the compounds producing increased turnover of dopamine in the striatum were in the same range as those displacing the in vivo binding of [3H]spiperone in the striatum. In addition, for all the compounds tested in the study, an increase in the turnover of dopamine to about 300% of control was observed for doses antagonising the stereotypy produced by the dopamine agonist, apomorphine. On the other hand, no consistent relationship between increased turnover of dopamine and the doses of the compounds required to antagonise apomorphine-induced hyperactivity was found. This result was also found in limbic areas. Remoxipride and haloperidol had little or no effect on the turnover of dopamine in either the hypothalamus or substantia nigra at the ED50 doses of these compounds for antagonism of apomorphine-induced stereotypy.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D001549:Benzamides; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid