Pramipexole is an agonist of dopamine receptors that has applications in Parkinson’s disease and other disorders.1,2,3,4 Pramipexole is usually available as a mixture of enantiomers, with the majority of the dopamine receptor-dependent activity resulting from the (S) form.5 (R)-Pramipexole is an enantiomer of pramipexole that is ~100-fold less active than the (S) form as a dopamine receptor agonist.5,6 For this reason, it can be used as a negative control for the (S) form in the study of dopamine receptors. Both isoforms are antioxidants that target mitochondria to prevent apoptosis.5,7,8,9 This cytoprotective effect of (R)-pramipexole, without dopaminergic side effects, suggests utility in amyotrophic lateral sclerosis.5,10
1.Hametner, E.M., Seppi, K., and Poewe, W.Role and clinical utility of pramipexole extended release in the treatment of early Parkinson's diseaseClin. Interv. Aging783-88(2012) 2.Kvernmo, T., H?rtter, S., and Bürger, E.A review of the receptor-binding and pharmacokinetic properties of dopamine agonistsClin. Ther.28(8)1065-1078(2006) 3.Millan, M.J., Maiofiss, L., Cussac, D., et al.Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypesJ. Pharmacol. Exp. Ther.303(2)791-804(2002) 4.Newman-Tancredi, A., Cussac, D., Audinot, V., et al.Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D2-like receptor and α1/α2-adrenoceptorJ. Pharmacol. Exp. Ther.303(2)805-814(2002) 5.Danzeisen, R., Schwalenstoecker, B., Gillardon, F., et al.Targeted antioxidative and neuroprotective properties of the dopamine agonist pramipexole and its nondopaminergic enantiomer SND919CL2x [(+)2-amino-4,5,6,7-tetrahydro-6-Lpropylamino-benzathiazole dihydrochloride]JPET316(1)189-199(2006) 6.Chang, W.I., Weber, M., Breier, M.R., et al.Stereochemical and neuroanatomical selectivity of pramipexole effects on sensorimotor gating in ratsBrain Res.143769-76(2012) 7.Ferrari-Toninelli, G., Maccarinelli, G., Uberti, D., et al.Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexoleBMC Pharmacol.10(2)1-6(2010) 8.Abramova, N.A., Cassarino, D.S., Khan, S.M., et al.Inhibition by R(+) or S(-) pramipexole of caspase activation and cell death induced by methylpyridinium ion orβamyloid peptide in SH-SY5Y neuroblastomaJ. Neurosci. Res.67(4)494-500(2002) 9.Gu, M., Iravani, M.M., Cooper, J.M., et al.Pramipexole protects against apoptotic cell death by non-dopaminergic mechanismsJ. Neurochem.91(5)1075-1081(2004) 10.Cheah, B.C., and Kiernan, M.C.Dexpramipexole, the R(+) enantiomer of pramipexole, for the potential treatment of amyotrophic lateral sclerosisIDrugs.13(12)911-920(2010)