Dexpramipexole dihydrochloride

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)