22260-51-1

Basic information

• Product Name: Bromocriptine mesylate
• Synonyms: (5'A)-2-BROMO-12'-HYDROXY-2'-(1-METHYLETHYL)-5'-(2-METHYLPROPYL)ERGOTAMAN-3',6',18-TRIONE MESYLATE;(+)-2-BROMO-12'-HYDROXY-2'-(1-METHYLETHYL)-5'-(2-METHYLPROPYL)-ERGOTAMAN-3',6',18-TRIONE METHANESULFONATE;(+)-2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)ergotaman-3',6'-18-trione methanesulfonate salt;2-BROMO-12'-HYDROXY-2'-(1-METHYLETHYL)-5'-(2-METHYL-PROPYL)ERGOTAMAN-3',6',18-TRIONE-METHANESULFONATE;2-BROMOERGOCRYPTINE MONOMETHANESULFONATE SALT;2-BROMO-ALPHA-ERGOCRYPTINE METHANESULFONATE;2-BROMO-ALPHA-ERGOCRYPTINE METHANESULFONATE SALT;BCT
• CAS NO: 22260-51-1
• Molecular Formula: CH₄O₃S*C₃₂H₄₀BrN₅O₅
• Molecular Weight: 750.7
• EINECS: 244-881-1
• Product Categories: Dopamine receptor;Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;PARLODEL
• Mol File: 22260-51-1.mol
• Article Data: 1

Chemical Properties

• Melting Point: 192-196° (dec)
• Boiling Point: 891.3 °C at 760 mmHg
• Flash Point: 492.8 °C
• Appearance: white/solid
• Vapor Pressure: 0mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: H2O: 0.8 mg/mL
• PKA: 4.90(at 25℃)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months
• Merck: 13,1400
• BRN: 4115238
• CAS DataBase Reference: Bromocriptine mesylate(CAS DataBase Reference)
• NIST Chemistry Reference: Bromocriptine mesylate(22260-51-1)
• EPA Substance Registry System: Bromocriptine mesylate(22260-51-1)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 22-24/25-36
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• RTECS: KE1595000
• F: 3-10
• Hazardous Substances Data: 22260-51-1(Hazardous Substances Data)

Usage

Description

Bromocriptine is a dopamine receptor agonist (Kis = 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-HT1A and 5-HT1D (Kis = 12.9 and 10.7 nM, respectively), as well as α1-adrenergic receptors (Kis = 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.

Chemical Properties

Solid

Originator

Parlodel,Sandoz,UK,1975

Uses

Different sources of media describe the Uses of 22260-51-1 differently. You can refer to the following data:
1. Dopamine receptor agonist; derivative of the ergotoxin group of ergot alkaloids. Prolactin inhibitor; antiparkinsonian.
2. 2-Bromo-α-Ergocryptine is a dopamine receptor agonist. 2-Bromo-α-Ergocryptine is a derivative of the ergotoxin group of ergot alkaloids. 2-Bromo-α-Ergocryptine is a prolactin inhibitor; antiparkinsoni an.
3. 2-Bromo-α-ergocryptine methanesulfonate salt has been used:as D2 agonist in bird zebra finchesfor Prl secretion inhibitor in micefor the inhibition of motility in planaria worm

Manufacturing Process

A solution of 3.4 grams of N-bromosuccinimide in 60 cc of absolute dioxane is added drop wise in the dark, during the course of 5 minutes, to a stirred solution, heated to 60°C, of 9.2 grams of ergocryptine in 180 cc of absolute dioxane. The reaction mixture is stirred at this temperature for 70 minutes and is concentrated to a syrup-like consistency in a rotary evaporator at a bath temperature of 50°C. The reaction mixture is subsequently diluted with 300 cc of methylene chloride, is covered with a layer of about 200 cc of a 2 N sodium carbonate solution in a separating funnel and is shaken thoroughly. The aqueous phase is extracted thrice with 100 cc amounts of methylene chloride. The combined organic phases are washed once with 50 cc of water, are dried over sodium sulfate and the solvent is removed under a vacuum. The resulting brown foam is chromatographed on a 50-fold quantity of aluminum oxide of activity II-III with 0.2% ethanol in methylene chloride as eluant, whereby the compound indicated in the heading is eluted immediately after a secondary fraction which migrates somewhat more rapidly than the fractions containing the heading compound. The last fractions to leave the aluminum oxide contain varying amounts of starting material together with the heading compound, and may be subjected directly, as mixed fractions, to an afterbromination in accordance with the method described above. The fractions containing the pure heading compound are combined and crystallized from methyl ethyl ketonehopropy1 ether. Melting point 215°-218°C (decomp.), [α]D 20-195° (c = 1 in methylene chloride).

Brand name

Parlodel (Novartis).

Therapeutic Function

Prolactin inhibitor

General Description

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 (pKa’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.

Biological Activity

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).

Biochem/physiol Actions

Bromocriptine is an ergot alkaloid and a dopamine D2 receptor agonist. It is prescribed for Parkinson′s disorder, hyperprolactinemia and galactorrhoea. It modulates β cells of the pancreas from insulin hypersecretion and improves the metabolic profile in type 2 diabetes patients with obesity. It also modulates glutamate release by glutamate transporter,GLT-1.

Veterinary Drugs and Treatments

Bromocriptine may potentially be of benefit in treating acromegaly/ pituitary adenomas or pseudopregnancy in a variety of species. However, because of adverse effects, its potential value for treating hyperadrenocorticism in dogs is low. It has been used in dogs for pregnancy termination and pseudopregnancy.

References

1) Nilsson and Hokfelt (1978), Effect of the dopamine agonist bromocriptine on blood pressure, catecholamines and renin activity in acromegalics at rest, following exercise, and during insulin induced hypoglycemia; Acta Endocrinol., Supp. 216 83 2) Seeman and Van Tol (1994), Dopamine receptor pharmacology; Trends Pharmacol. Sci., 15 264 3) Carvalho et al. (2015), Maternal prolactin inhibition causes changes in leptin at 22- and 30-day old pups; Horm. Metab. Res., 47 528 4) Hubner and Koob (1990), Bromocriptine produces decreases in cocaine self-administration in the rat; Neuropsychopharmacol., 3 101

InChI:InChI=1/C32H40BrN5O5.CH4O3S/c1-16(2)12-24-29(40)37-11-7-10-25(37)32(42)38(24)30(41)31(43-32,17(3)4)35-28(39)18-13-20-19-8-6-9-22-26(19)21(27(33)34-22)14-23(20)36(5)15-18;1-5(2,3)4/h6,8-9,13,16-18,23-25,34,42H,7,10-12,14-15H2,1-5H3,(H,35,39);1H3,(H,2,3,4)/t18?,23-,24?,25+,31-,32?;/m1./s1

Upstream product

• 75-75-2 methanesulfonic acid 
• 25614-03-3 Bromocriptine 

Relevant articles and documents

Preparation method of bromocriptine mesylate

The invention relates to a preparation method of bromocriptine mesylate. The preparation method comprises the following steps of: dissolving bromocriptine with methanol, dropwisely adding a newly prepared methanesulfonic acid water solution with the molar weight 1.1-1.5 times that of the bromocriptine under a stirring condition, continuing stirring for 10-40 minutes, cooling to 0 DEG C and to roomtemperature, performing filtering to obtain a solid, recrystallizing the solid with ethanol once, performing filtering and drying so as to obtain bromocriptine mesylate.