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Talipexole

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Talipexole

Talipexole
Systematic (IUPAC) name
6-allyl-5,6,7,8-tetrahydro-4H-[1,3]thiazolo[4,5-d]azepin-2-amine
Clinical data
AHFS/Drugs.com
Legal status
  • Prescription only
Routes Oral
Identifiers
CAS number  N
ATC code None
PubChem
ChemSpider  N
UNII  N
ChEMBL  N
Chemical data
Formula C10H15N3S 
Mol. mass 209.31 g/mol
 N   

Talipexole (B-HT920) is a dopamine agonist that has been proposed as an antiparkinsonian agent.[1] It also has α1-adrenergic and α2-adrenergic agonist activity.[2]

Mechanism of Action

Talipexole is a dopamine receptor agonist (D2 in specific) and this drug interacts both pre- and post-synaptic receptors. The drug action is also shown to have an effect on the α2-adrenergic. Primate models of Parkinson's disease show improved symptoms; this effect was increased further when this drug is combined with levodopa therapy. The clinical trials have shown statistically significant improvements for symptoms including akinesia, rigidity, tremor and gait disturbances.[3]

Phamacokinetic and Pharmacodynamic Profile

It is dosed once per day. The common adverse events include drowsiness, dizziness, hallucinations, minor reversible gastrointestinal symptoms. [3]The drug has undergone much study in vivo, in vitro, and in clinical trials. In a study of 12 volunteers, the below data was found. [4]

Property Data
Cmax (ng/mL) 0.95±0.12
Tmax (h) 1.38±0.91
T1/2 (h) 12.29±4.59

In Vitro Studies

In Vitro studies were conducted using rat brain tissue and demonstrated the binding to D2 receptors and α2-adrenoceptors, but not to other dopaminergic or adrenergic receptors.[5] The effect seen from talipexole involves inhibition of the electrically evoked release of dopamine, and acetylcholine supporting the evidence to the agonist effects observed.[6] Other supporting evidence for the agonist mechanism was found in the inhibition of N-methyl-D-aspartate (NMDA)-evoked release of noradrenaline.[7]

In Vivo Animal Studies

Many studies in animal models show that talipexole reduces dopamine synthesis and turnover in parts of the brain at certain concentrations. Mice have demonstrated similar agonist effects as shown by their increased motor activity and rearing/sniffing. [3] In normal marmoset monkeys, higher doses from 80-160 µg/kg i.p. produced a dose dependent increase in motor activity and the lowest dose of 20 µg/kg i.p. depressed motor activity.[8]

Clinical Trials

  • Parkinson's Disease- Many studies found the potential for effective treatment with this drug. Clinical trials have moved to pramipexole. One Patent is held that claims to have a drug delivery system comprising a therapeutically effect amount of anti-parkinson agent like talipexole, at least one skin penetration enhancer that is effectively a sunscreen, and at least one volatile liquid.[9]
  • Tic disorders- Study found that talipexole has no effective role in the regular management of tic disorders at tolerable dosages.[10]
  • Pain and inflammation-There is even a patent currently out for alpha adrenergic receptor agonists in the treatment of pain and/or inflammation. [11]

FDA Regulations

Currently following regulations for structured product labeling set by FDA for substances. ( FDA Industry Substance Indexing


References

  1. ^ Kitamura Y, Kosaka T, Kakimura JI, et al. (December 1998). "Protective effects of the anti-parkinsonian drugs talipexole and pramipexole against 1-methyl-4-phenylpyridinium-induced apoptotic death in human neuroblastoma SH-SY5Y cells". Mol. Pharmacol. 54 (6): 1046–54.  
  2. ^ Van der Laan JW (February 1987). "Dopaminergic and alpha 1-adrenergic properties of B-HT920 revealed in morphine-dependent rats". Pharmacology, Biochemistry, and Behavior 26 (2): 265–9.  
  3. ^ a b c Plosker, Greg; Benfield, Paul (May 1997). "Talipexole". CNS Drugs (ADIS) 7 (5): 410–416.  
  4. ^ Zhang, T.; Song, M.; Hang, T.; Xu, X.; Wen, A.; Yang, L.; Jia, L. (2009). "Pharmacokinetic profile of talipexole in healthy volunteers is not altered when it is co-administered with Madopar (co-beneldopa)". Journal of Clinical Pharmacy and Therapeutics 34 (3): 345–354. 
  5. ^ Hashimoto, T.; Kuriyama, K.; Kohno, Y. (1993). "Effect of talipexole dihydrochloride (B-HT 920 CL2), bromocriptine mesylate and SND 919 on cerebral GABAergic and glutamatergic neurons". The Clinical Report 27 (13): 77–87. 
  6. ^ Krukarch, B.; Schepens, E.; Dolleman-Van Der, W. (1990). "Lack of a dopamine autoreceptor selective profile of B-HT 920 in functional in vitro model systems of D2 receptors in rat striatum.". Eur J Pharmacol 187: 257–269. 
  7. ^ Fink, K.; Gothert, M.; Kohno, Y. (1993). "Modulation of N-methyl-D-aspartate (NMDA)-stimulated noradrenaline release in rat brain cortex by presynaptic α2-adrenoceptors.". Naunyn Schmiedebergs Arch Pharmacol 348: 502–507. 
  8. ^ Irifune, M.; Nomoto, M.; Fukuda, T. (1993). "Effects of talipexole on motor behavior in normal and MPTP-treated common marmosets.". Eur. J. Pharmacol. 238: 235–240. 
  9. ^ US patent 6.929.801, Klose, "Transdermal delivery of antiparkinson agents", issued 2005-Aug-16 
  10. ^ Goetz, C. (1994). "Talipexole and adult Gilles de la Tourette's syndrome: double-blind, placebo-controlled clinical trial.". Mov. Disord. 3: 315–7. 
  11. ^ US patent 8.889.173, Zanella, "Alpha adrenergic receptor agonists for treatment of pain and/or inflammation", issued 2009-Oct-22 


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