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 mesylate, also known as Parlodel, is a dopamine receptor agonist belonging to the ergotoxin group of ergot alkaloids. It is a white solid that is soluble in ethanol and slightly soluble in water. Bromocriptine mesylate is characterized by its rapid absorption after oral administration, quick entry into the brain with a short half-life, and low systemic bioavailability due to extensive first-pass metabolism. It is used to treat various conditions, including Parkinson's disease, hyperprolactinemia-associated dysfunctions, and acromegaly. The drug also has the potential for interactions with other medications, such as DA antagonists, highly plasma protein-bound drugs, macrolides antibacterials, and caffeine.

Uses

1. Used in Pharmaceutical Industry:
Bromocriptine mesylate is used as a dopamine receptor agonist for the treatment of Parkinson's disease. It helps restore locomotor activity without inducing dyskinesia in patients.
2. Used in Endocrinology:
Bromocriptine mesylate is used as a prolactin inhibitor for the management of hyperprolactinemia-associated dysfunctions, such as infertility and menstrual disorders.
3. Used in Neurology:
Bromocriptine mesylate is used as an antiparkinsonian agent to alleviate the symptoms of Parkinson's disease by providing more continuous stimulation of dopamine receptors.
4. Used in Gastroenterology:
Bromocriptine mesylate is used as a treatment for acromegaly, a condition characterized by excessive growth hormone production, by reducing the levels of growth hormone in the body.
5. Used in Veterinary Medicine:
Bromocriptine mesylate is used as a D2 agonist in bird zebra finches for the inhibition of prolactin secretion.
6. Used in Research:
Bromocriptine mesylate is used as a research tool for studying the effects of dopamine receptor agonists on various biological processes and for the development of new drugs targeting dopamine receptors.

Originator

Parlodel,Sandoz,UK,1975

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).

Therapeutic Function

Prolactin inhibitor

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.