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.

mechanism of action

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.

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

route of 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.

drug interactions

Cimetidine: Cimetidine may increase the effect and toxicity of pramipexole.

Paliperidone: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, pramipexole. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Thiothixene: Thiothixene may antaonize the effects of the anti-Parkinsonian agent, Pramipexole. Consider alternate therapy or monitor for decreased effects of both agents.

Triprolidine: The CNS depressants, Triprolidine and Pramipexole, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Ziprasidone: The atypical antipsychotic, ziprasidone, may antagonize the effect of the dopamine agonist, pramipexole. Consider alternate therapy or monitor for worsening of movement disorder.

Zuclopenthixol: Antagonism may occur between zuclopenthixol, a dopamine D2 receptor antagonist, and pramipexole, a dopamine agonist. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of both agents if concurrent therapy is initiated, discontinued or dose(s) changed.