Interaction of non-steroidal antiestrogens with dopamine receptor binding.
The ability of various estrogen antagonists and agonists to compete with [3H]spiroperidol, [3H]domperidone, [3H]dihydroalprenolol, [3H]dihydroergocryptine, [3H]dopamine or [3H]5-hydroxytryptamine for binding to membrane preparations from rat brain tissue was tested. The non-steroidal triphenylethylene-type antiestrogens with an amine side chain--enclomiphene, nitromifene, tamoxifen and zuclomiphene--were found to be competitive inhibitors of [3H]spiroperidol (Kd = 0.12 nM; Bmax = 101 fmol/mg protein) and [3H]domperidone (Kd = 0.62 nM; Bmax = 86 fmol/mg protein) binding to striatal membranes. The Ki values ranged from 4-12 microM. Estradiol-17 beta (Ki = 480 microM) or diethylstilbestrol (Ki = 63 microM) were much less effective inhibitors exhibiting noncompetitive interaction with the in vitro binding of [3H]spiroperidol. The pharmacological relevance of the antiestrogen interactions with dopamine receptor binding is discussed with respect to adverse effects of the in vivo administered compounds such as nausea and vomiting.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism; D004088:Dihydroergotoxine / Q000378:metabolism; D004294:Domperidone / Q000378:metabolism; D004965:Estrogen Antagonists / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
D004965:Estrogen Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D004088:Dihydroergotoxine; D013134:Spiperone; D004294:Domperidone; D004082:Dihydroalprenolol