title: Evidence for an irreversible interaction of bromocryptine with central dopamine receptors.
abstract: The effects of the dopamine agonist bromocryptine on several measures dopaminergic function were assessed in the rat. Following  inhibition of impulse flow with gamma-butyrolactone, and after dopa decarboxylase inhibition, dopa accumulation and its reversal by dopamine agonists is easily studied. In this model, bromocryptine (10 mg/kg, i.p.) caused a significant decrease in dopa accumulation in both the striatum and olfactory tubercle which was prevented, but not reversed, by the dopamine antagonist (+)-butaclamol (4 mg/mg, i.p.). The inactive isomer, (-)-butaclamol was without effect. Analysis of an vitro 3H-spiperone binding 2h after bromocryptine (10 mg/kg, i.p.) revealed a 30% decrease in the number of striatal dopamine receptors labelled (Bmax), with no change in receptor affinity for 3H-spiperone. No changes in binding were seen when animals were sacrificed 30 min or 48 h after bromocryptine. In extracellular single unit recording experiments, bromocryptine-induced depression of nigrostriatal dopamine cell firing was found to be largely reversible by the dopamine antagonist haloperidol when injected within 5 min of intravenous bromocryptine. However, when haloperidol was injected more than 20 min after bromocryptine, no reversal of bromocryptine-induced depression of cell firing was obtained. These results strongly suggest that bromocryptine interacts in an irreversible fashion with central dopaminergic receptors.
mesh_terms: D015107:4-Butyrolactone / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001971:Bromocriptine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism; D004594:Electrophysiology; D007700:Kinetics; D008297:Male; D009830:Olfactory Bulb / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D011954:Receptors, Dopamine; D001971:Bromocriptine; D013134:Spiperone; D014446:Tyrosine 3-Monooxygenase; D004296:Dopa Decarboxylase; D015107:4-Butyrolactone