Bromocriptine mesylate [Dopamine D2 Receptor; Dopamine D3 Receptor Agonist]

A highly potent and selective D2-like receptor agonist (Ki values of D2, D3, D5 and D1 receptors are 5.3, 7.4, 454 and 645 nM, respectively). Prototype anti-Parkinson's disease agent. The modulator is active in vivo.

(5'a)-2-Bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)ergotaman-3',6',18-trione mesylate

Agonist

Parkinson's Disease

Bromocriptine stimulates [35S]-GTPγS binding on the D2 dopamine receptor expressed in CHO cells with a pEC50 of 8.15±0.05 [1]. Bromocriptine is also a strong inhibitor of nitric oxide synthase in the brain. Ergot alkaloid bromocriptine (BKT) was found to be a potent inhibitor of purified neuronal nitric oxide synthase (NOS) (IC50 = 10±2 μM), while it is effective against inducible macrophages NOS (IC50> 100 μM) The activity is weak [2]. Bromocriptine inhibits the activity of at least one human cytochrome P450 enzyme. Bromocriptine is a potent CYP3A4 inhibitor with an IC50 value of 1.69 μM for its interaction [3].

[1]. Gardner B, et al. Agonist action at D2(long) dopamine receptors: ligand binding and functional assays. Br J Pharmacol. 1998 Jul;124(5):978-84.

[2]. Renodon A, et al. Bromocriptine is a strong inhibitor of brain nitric oxide synthase: possible consequences for the origin of its therapeutic effects.FEBS Lett. 1997 Apr 7;406(1-2):33-6.

[3]. Wynalda MA, et al. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos. 1997 Oct;25(10):1211-4.

In the forced swimming test (FST) and tail suspension test (TST), each group of mice was administered bromocriptine mesylate (2 mg/kg, i.p.). Compared with the control group, the bromocriptine group showed a significant anti-fixation effect. When taking bromocriptine 30 minutes 7 days after the last dose of MPE treatment and FST, this dopaminergic agonist produced a significant dose of MPE (200 mg/kg, po) compared to MPE treatment alone Dependence enhancement. Compared with the control group, the fixed time of the bromocriptine treatment group was significantly reduced. Compared with MPE treatment alone, pretreatment with MPE (100 and 200 mg/kg, po.) 7 days after taking bromocriptine showed a significant dose-dependent and enhanced dose-dependent anti-fixation effect of MPE [4 ]. Compared with sham surgery (saline-injected rats), the intrathoracic administration of bromocriptine significantly reduced the static mechanical allodynia (SMA) score, and its effect lasted for 30 minutes. Compared with sham operation, intraperitoneal administration of bromocriptine resulted in a significant pain score, a dose-dependent (0.1 mg and 1 mg/kg) reduction in the CCI-IoN group, and lasted 6 hours. The highest dose caused the highest score to decrease (P<0.01). The effect of bromocriptine lasts 20 minutes. Compared with the sham operation group, intraperitoneal administration of bromocriptine resulted in a significant dose-dependent decrease in the SMA score of the CCI-IoN + 6-OHDA injury group. The effect lasts 6 hours [5].

[1]. Gardner B, et al. Agonist action at D2(long) dopamine receptors: ligand binding and functional assays. Br J Pharmacol. 1998 Jul;124(5):978-84.

[2]. Renodon A, et al. Bromocriptine is a strong inhibitor of brain nitric oxide synthase: possible consequences for the origin of its therapeutic effects.FEBS Lett. 1997 Apr 7;406(1-2):33-6.

[3]. Wynalda MA, et al. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos. 1997 Oct;25(10):1211-4.

[4]. Rana DG, et al. Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu. 2014 Jan;35(1):90-7.

[5]. Dieb W, et al. Nigrostriatal dopaminergic depletion increases static orofacial allodynia. J Headache Pain. 2016;17:11.

750.7

C32H40BrN5O5.CH3SO3H

[H][C@]4([C@@](N[C@]([C@H](C)C)5C(N([C@@]([H])(CC(C)C)C(N(CCC7)[C@@]76[H])=O)[C@@]6(O)O5)=O)=O)CN([C@](C3=C4)([H])CC1=C(Br)NC2=C1C3=CC=C2)C.CS(=O)(O)=O

DMSO and Ethanol

pKi: 8.05±0.2 (dopamine D2 receptor)

22260-51-1

31100

>98%

Room temperature

Room Temperature

For research use only

DRD2

DRD2

The dopamine receptor D2, also known as D2R, is a protein encoded by the DRD2 gene in humans. The dopamine D2 receptor is the main receptor for most antipsychotic drugs. The structure of DRD2 combined with the atypical antipsychotic drug risperidone has been determined.

This gene encodes the D2 subtype of the dopamine receptor, which is coupled to the Gi subtype of the G protein-coupled receptor. This G protein-coupled receptor can inhibit the activity of adenylate cyclase.

In mice, the modulation and exploration of D2R surface expression by neurocalcium sensor 1 (NCS-1) in the dentate gyrus is related to synaptic plasticity and memory formation. A recent study showed that D2R has a potential role in restoring forearm cortical fear memory.

In Drosophila, activation of D2 autoreceptors protects dopamine neurons from MPP+-induced cell death, a toxin that mimics the pathology of Parkinson's disease.