Pergolide mesylate salt Chemical Properties

Melting point:

252-254°C

alpha 

aD20 between -18.0° and -23.0° (c = 10 mg/ml in DMF)

storage temp. 

Inert atmosphere,Store in freezer, under -20°C

solubility 

ethanol: soluble2mg/mL

form 

solid

pka

pKa (66% DMF) 7.8(at 25℃)

color 

white

optical activity

[α]20/D 35°, c = 0.2 in pyridine(lit.)

InChIKey

UWCVGPLTGZWHGS-PLBOZXOQNA-N

SMILES

C12=C3C=CC=C1[C@@]1([H])C[C@H](CN(CCC)[C@]1([H])CC2=CN3)CSC.S(=O)(=O)(O)C |&1:6,9,15,r|

CAS DataBase Reference

66104-23-2(CAS DataBase Reference)

Safety Information

Hazard Codes 

T+

Risk Statements 

28

Safety Statements 

28-36/37-45

RIDADR 

UN 1544

WGK Germany 

3

RTECS 

KE6345000

HS Code 

2939690000

Pergolide mesylate salt Usage And Synthesis

Description

Pergolide mesylate is a potent, long-acting dopamine agonist useful in the treatment of Parkinson’s disease and hyperprolactinemia, Compared with lergotrile, pergolide mesylate has shown less toxicity and lower propensity for inducing psychosis.

Description

Pergolide is a potent dopamine D₁ and D₂ receptor agonist (K_is = 111 and 0.495 nM, respectively, for rat striatal receptors). It depresses dopaminergic firing in paralyzed rats (ED₅₀ = <20 μg/kg), an effect that can be reversed by the dopamine D₂-selective antagonist spiperone or the dopamine D₁-selective antagonist SCH 23390 . Pergolide (0.025 and 0.05 mg/kg) increases the volume threshold for inducing bladder contraction in a cynomolgus monkey model of Parkinson''s disease induced by MPTP. It also reduces carrageenan-induced paw edema in adrenalectomized rats (ED₅₀ = 0.4 mg/kg).

Chemical Properties

White to Off-White Solid

Originator

Lilly (USA)

Uses

A dopaminergic agonist that also decrease plasma prolactin concentrations. An antiparkinsonian agent

Uses

glucocorticoid, antiinflammatory

Uses

dopamine receptor agonist, anti-Parkinson's agent

Definition

ChEBI: A methanesulfonate salt obtained from pergolide by mixing eqimolar amount of pergolide and methanesulfonic acid. A dopamine D2 receptor agonist which also has D1 and D2 agonist properties, it i used in the management of Parkinson's disease, although it was withdrawn from the U.S. and Canadian markets in 2007 due to an increased risk of cardiac valve dysfunction.

Manufacturing Process

Dimethyl disulfide (73.6 ml, 0.79 mol) and tri-n-butylphosphine (79.6 ml, 0.32 mol) were added to a solution of 9,10-dihydrolysergol in (8.1 g, 0.032 mol) in the 150 ml of anhydrous DMF and were stirred at room temperature for 6 hours under a nitrogen atmosphere. Dimethyl disulfide of the reaction mixture was removed under vacuo. A solution of the residue in ethyl acetate was extracted with 3.7% HCl (aq.). The aqueous layer was basified with ammonium hydroxide to a pH of 10 and then extracted with ethyl acetate. Removal of ethyl acetate followed by a silica gel column purification eluting with 10% MeOH/CH2Cl2 gave5.5.g of D-6-methyl-8β(methylthiomethyl)ergoline (60%).
A solution of D-6-methyl-8β-(methylthiomethyl)ergoline (0.4 g, 0.0014 mol) and NaI (0.63 g, 0.0042 mol) in 10 ml of propionic anhydride was refluxed for 40 hours. The reaction mixture was guenched with a 10% Na2CO3 solution and extracted by ethyl acetate. The combined organic layers were washed with a saturated brine solution, dried with magnesium sulfate and concentrated to produce oil. The oil was purified by silica gel column, eluting with 10% MeOH/CH2Cl2 to give 0.33 g of D-1,6-dipropionyl-8β(methylthiomethyl)ergoline.
LiAlH4 (0.6 g, 0.0156 mol) was slowly added to a solution of D-1,6dipropionyl-8β-(methylthiomethyl)ergoline in the 20 ml anhydrous THF at 0°C under nitrogene atmosphere. The mixture was stirred at 0°C for 30 min and then at room temperature for 4 hours. The reaction was cooled to 0°C and 0.6 ml of water was slowly added. The mixture was stirred at 0°C for 10 min and 1.8 ml of 15% NaOH (aq.) and 2.5 ml of water were added respectively. The mixture was stirred for 30 min at room temperature and then filtered. Excess of the solvent was removed under reduced pressure to give 150 mg of 8β-((methylthio)methyl)-6-propyl-ergoline or pergolide (yield: 68%). Ergoline,8-((methylthio)methyl)-6-propyl-, monomethanesulfonate, (8β)- may be prepared by mixing of components in solution.

brand name

Permax (Valeant).

Therapeutic Function

Dopamine agonist

Biochem/physiol Actions

Dopaminergic agonist; suppresses pituitary secretion of prolactin; anti-Parkinsonian agent.

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