Synthesis of new haloperidol analogues and characterization of their interactions with alpha-adrenoceptors in rat parotid slices and human platelet membranes.
1 The synthesis of several butyrophenone analogues of haloperidol is described. 2 The effects of these compounds on alpha-adrenoceptors were evaluated by examining their ability to reduce alpha 1-stimulated K+ release from rat parotid slices and to displace [3H]-phentolamine from human platelet membrane alpha 2-adrenoceptors. 3 The affinity of haloperidol and its analogues for alpha 1-receptors was found to be 1 to 2 orders of magnitude greater than that for alpha 2-adrenoceptors. These observations suggest that most of the alpha-adrenoceptor activity of butyrophenones results from their interaction with alpha 1-adrenoceptors. 4 The relatively high affinity of the butyrophenones for alpha 1-adrenoceptors suggests that they may be useful as probes in studies of alpha 1-adrenoceptors in these and other tissues.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010306:Parotid Gland / Q000378:metabolism*; D010646:Phentolamine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D006220:Haloperidol; D011188:Potassium; D010646:Phentolamine