Pergolide Mesylate (Permax; Pergotoliderived; LY127809; LY-127809), the mesylate salt of Pergolide, is a novel and potent antiparkinsonian agent which acts as a dopaminergic agonist. It is used to treat Parkinson's disease in certain nations. The dopamine D2, D1, and serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT2C receptors are all agonist-activated by pergolide mesylate. It might also, like cabergoline, have agonist activity at other dopamine receptor subtypes.

Physicochemical Properties

Molecular Formula	C20H30N2O3S2
Molecular Weight	410.59
Exact Mass	410.169
Elemental Analysis	C, 58.51; H, 7.36; N, 6.82; O, 11.69; S, 15.62
CAS #	66104-23-2
Related CAS #	Pergolide; 66104-22-1; Pergolide-d7 mesylate
PubChem CID	47812
Appearance	Solid powder
Boiling Point	491.3ºC at 760 mmHg
Melting Point	252-254°C
Flash Point	250.9ºC
LogP	4.793
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	480
Defined Atom Stereocenter Count	3
SMILES	[H][C@@]1(N(CCC)C[C@H](CSC)C[C@@]12[H])CC3=CNC4=CC=CC2=C43.CS(=O)(O)=O
InChi Key	UWCVGPLTGZWHGS-ZORIOUSZSA-N
InChi Code	InChI=1S/C19H26N2S.CH4O3S/c1-3-7-21-11-13(12-22-2)8-16-15-5-4-6-17-19(15)14(10-20-17)9-18(16)21;1-5(2,3)4/h4-6,10,13,16,18,20H,3,7-9,11-12H2,1-2H3;1H3,(H,2,3,4)/t13-,16-,18-;/m1./s1
Chemical Name	(6aR,9R,10aR)-9-(methylsulfanylmethyl)-7-propyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline;methanesulfonic acid
Synonyms	LY127809; Pergolide methanesulfonate; LY-127809; LY 127809
HS Tariff Code	2934.99.03.00
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	D2 receptor; D1 Receptor
ln Vitro	In vitro activity: Pergolide treatment dose-dependently blocks H2O2-induced cell death in SH-SY5Y neuroblastoma cells. Pergolide, which acts at very low concentrations (nanomolar range) and in the very early stages of the neurotoxic intracellular process, protects SH-SY5Y neuroblastoma cells from cell death that is specifically induced by H2O2(2).
ln Vivo	Pergolide (0.3 mg/kg; intraperitoneal injection; daily; 11 days) treatment lowers the amount of working/reference memory errors in a rat model of Parkinson's disease induced by 6-OHDA. Pergolide enhances the oxidative balance of the brain and helps with spatial memory[3].
Cell Assay	Cell Line: SH-SY5Y cells Concentration: 0.01 μM, 0.1 μM, 0.5 μM, 1 μM, 5 μM, 10 μM, 50 μM Incubation Time: Pretreated for 2 hours Result: Dose-dependently inhibited H2O2-induced cell death in SH-SY5Y neuroblastoma cells.
Animal Protocol	Wistar rats (200-250 g) induced with 6-hydroxydopamine (6-OHDA) 0.3 mg/kg Intraperitoneal injection; daily; 11 days
References	[1]. Effectiveness of pergolide mesylate in long term treatment of hyperprolactinaemia. Br Med J (Clin Res Ed). 1983 Apr 9;286(6372):1177-9. [2]. Pergolide protects SH-SY5Y cells against neurodegeneration induced by H(2)O(2). Eur J Pharmacol. 2002 Jan 2;434(1-2):17-20. [3]. The effects of pergolide on memory and oxidative stress in a rat model of Parkinson's disease. J Physiol Biochem. 2012 Mar;68(1):59-69.
Additional Infomation	Pergolide mesylate is 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 is 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. It has a role as an antiparkinson drug, a dopamine agonist and a geroprotector. It contains a pergolide(1+). Pergolide Mesylate is a semi-synthetic ergot derivative and a dopamine agonist with antiparkinson property. Pergolide mesylate binds to and activates dopamine receptor subtypes D1 and D2, resulting in prolactin secretion inhibition, transient increase in serum concentration of growth hormone, and decrease in serum concentration of luteinizing hormone. Direct stimulation of postsynaptic dopamine receptors in the nigrostriatal system, may account for this agent's antiparkinson activity. A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES. See also: Pergolide (has active moiety).

Solubility Data

Solubility (In Vitro)

DMSO: ~10 mg/mL (~24.4 mM) Water: ~82 mg/mL (~199.7 mM) Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4355 mL	12.1776 mL	24.3552 mL
	5 mM	0.4871 mL	2.4355 mL	4.8710 mL
	10 mM	0.2436 mL	1.2178 mL	2.4355 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.