Bromocriptine mesylate

Описание

Bromocriptine is a dopamine receptor agonist (K_is = 1,659, 12.2, 12.2, 59.7, and 1,691 nM for dopamine D₁, D₂, D₃, D₄, and D₅ receptors, respectively). It also binds to the serotonin (5-HT) receptor subtypes 5-HT_1A and 5-HT_1D (K_is = 12.9 and 10.7 nM, respectively), as well as α₁-adrenergic receptors (K_is = 1.12-4.17 nM). Bromocriptine (5 mg/kg) restores locomotor activity, without inducing dyskinesia, in a macaque model of Parkinson’s disease induced by MPTP. Formulations containing bromocriptine have been used in the treatment of Parkinson''s disease, hyperprolactinemia-associated dysfunctions, and acromegaly.

Химические свойства

Solid

Использование

Dopamine receptor agonist; derivative of the ergotoxin group of ergot alkaloids. Prolactin inhibitor; antiparkinsonian.

Общее описание

Bromocriptine mesylate,(6aR,9R)-5-bromo-N-((2R,5S,10aS,10bS)-10b-hydroxy-5-isobutyl-2-isopropyl-3,6-dioxooctahydro-2H-oxazolo[3,2-a]pyrrolo[2,1c]pyrazin-2-yl)-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide methanesulfonate(Parlodel), is a white solid soluble in ethanol and slightly solublein water (pK_a’s＝6.6 and 15). Bromocriptine is rapidlyabsorbed after oral administration and it has low systemicbioavailability because of its extensive first-pass metabolism.Bromocriptine enters the brain quickly with a half-lifefor uptake into the brain of approximately 0.3 hours; 8% ofthe drug crosses the BBB.The metabolites are excreted primarilyin the bile and feces. The high first-pass hepatic metabolismimplies an increased risk of drug interactions.Concomitant administration with the DA antagonists, metoclopramide,or domperidone may aggravate parkinsoniansymptoms and induce extrapyramidal side effects (EPS).Other drugs that may interact with bromocriptine are highlyplasma protein–bound drugs (e.g., warfarin, increased dyskinesiacaused by bromocriptine); macrolides antibacterials(enhanced dopaminergic effects); and caffeine (elevation inplasma bromocriptine concentrations). The combination oflevodopa/AADC inhibitors with bromocriptine permits a reductionof the dose of levodopa. Thus, the side effects oflevodopa are decreased, resulting in a more continuous stimulationof DA receptors.

Биологическая активность

Selective D 2 -like dopamine receptor agonist (K i values are ~ 8, ~ 5, ~ 290, ~ 440 and ~ 450 nM for D 2 , D 3 , D 4 , D 1 and D 5 receptors respectively).