Pramipexole is a medication indicated for treating Parkinson's disease and restless legs syndrome (RLS). It is also sometimes used off-label as a treatment for cluster headache or to counteract the problems with low libido experienced by some users of SSRI antidepressant drugs. Pramipexole has shown robust effects on pilot studies in bipolar disorder. Pramipexole is classified as a non-ergoline dopamine agonist.
Indication
For the treatment of signs and symptoms of idiopathic Parkinson's disease
Pharmacology
Pramipexole is a nonergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. The relevance of D3 receptor binding in Parkinson's disease is unknown. The precise mechanism of action of Pramipexole as a treatment for Parkinson's disease is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that Pramipexole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum.
Affected Organisms
Humans and other mammals
Biotransformation
No metabolites have been identified in plasma or urine.
Absorption
Rapid. Absolute bioavailability is greater than 90%, indicating that pramipexole is well absorbed and undergoes little presystemic metabolism. Food does not affect the extent of absorption.
Half Life
8 hours
Protein Binding
About 15% bound to plasma proteins.
Elimination
Urinary excretion is the major route of pramipexole elimination, with 90% of a pramipexole dose recovered in urine, almost all as unchanged drug. Nonrenal routes may contribute to a small extent to pramipexole elimination, although no metabolites have been identified in plasma or urine.
Distribution
* 500 L
Clearance
* renal cl=400 mL/min
References
•
Mierau J, Schneider FJ, Ensinger HA, Chio CL, Lajiness ME, Huff RM: Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur J Pharmacol. 1995 Jun 23;290(1):29-36.
[Pubmed]
The opposite enantiomer of Pramipexole (P700755), a dopamine-D2-receptor agonist. Dexpramipexole is a low-molecular-weight, water-soluble, orally bioavailable, renally excreted compound with linear pharmacokinetics.
参考文献
PubChem文献
数据源提供
• Mierau J, Schneider FJ, Ensinger HA, Chio CL, Lajiness ME, Huff RM: Pramipexole binding and activation of cloned and expressed dopamine D2, D3 and D4 receptors. Eur J Pharmacol. 1995 Jun 23;290(1):29-36. Pubmed
• Mierau, J., et al.: J. Med. Chem., 30, 494 (1987)
