Ergolines pergolide

The ergolines have provided a number of drugs that show interaction with neurotransmitters. Depending on the substitution pattern, they may be dopamine agonists or antagonists, a-adrenergic blockers, or Inhibitors of the release of prolactin. A recent member of the series, pergolide... 

LiAIH4 (0.6 g, 0.0156 mol) was slowly added to a solution of D-1,6-dipropionyl-8p-(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 8p-((methylthio)methyl)-6-propyl-ergoline or pergolide (yield 68%). Ergoline,... 

In contrast to the tricyclic partial ergolines, the tetracyclic ergolines such as d-LSD (pK =8.7), lisuride (pKj=9.1) or pergolide (pKj=8.7) bind with high affinity to 5-HT1A receptors but they lack selectivity. 

Pergolide mesylate is stable as the bulk drug substance stored at 25 C for up to 2 years and is also stable under stress conditions (100 C for 4 weeks/closed container, 3x10 lux-hr. light exposure, 65 C for 3 months, 40 Cy75% RH/closed container for 3 months, 25 C/75% RH/closed container for 3 months, and 40 C/75% RH/open container for 6 months). A trace level of (8P)-8-[(methylsulfinyl)methyl]-6-propyl-D-ergoline (the sulfoxide,... 

Misner, J.W, Kennedy, J.H. and Biggs, WS. (1997) Integration of a highly selective demethylation of a quaternized ergoline into a one-pot synthesis of pergolide. Org. Process Res. Develop., 1, 77—80. 

Figure 3 Structures of ergolines that show (partial) agonist activity at Da-like receptors. CY 208-243 is an agonist at Dj-like receptors, and pergolide shows mixed Dj-like and Da-like receptor agonist activity...

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