Talipexole Explained

Talipexole (B-HT920, Domnin) is a dopamine agonist that is marketed as a treatment for Parkinson's Disease in Japan by Boehringer Ingelheim; it was introduced in 1996.[1] As of December 2014 it was not approved for marketing in the US nor in Europe.[2]

Talipexole is a D2 dopamine receptor agonist and interacts with both pre- and post-synaptic receptors. It also is an α2-adrenergic agonist.[3]

The main side effects are drowsiness, dizziness, hallucinations and minor gastrointestinal complaints.[3] In Japan, Ministry of Health, Labour and Welfare mandated in 2008 that Boehringer add a warning to the label concerning the risk of sudden onset of sleep.[4]

Synthesis

The N-alkylation of azepan-4-one [105416-56-6] (1) with allyl bromide in the presence of potassium carbonate gives 1-allyl-azepan-4-one (2). This is halogenated with molecular bromine in acetic acid to give 1-allyl-5-bromohexahydro-4-azepinone (3). The last step involves cyclization with thiourea (4) in refluxing ethanol, completing the synthesis of talipexole (5).

See also

Notes and References

  1. PharmaLetter 22 July 1996 First Launch In Japan For Talipexole
  2. http://www.evaluategroup.com/Universal/View.aspx?type=Report&id={23D6C352-1933-41D7-A788-054D46E19AAA}&params=%3CPARAMS%20currencyId=%220%22%3E%3CPARAM%20linkKind=%221%22%20compId=%221019%22%20name=%22parkinson%20+disease%22%20itemId=%22125%22%20/%3E%3C/PARAMS%3E EvaluatePharma Database
  3. Benkert O, Müller-Siecheneder F, Wetzel H . Dopamine agonists in schizophrenia: a review . European Neuropsychopharmacology . 1995 . 5 Suppl . 43–53 . 10.1016/0924-977x(95)00022-h . 8775758 . 1600286 .
  4. Japanese Ministry of Health, Labour and Welfare March 2008 Pharmaceuticals and Medical Devices Safety Information No. 245