Pre-clinical studies of pramipexole: clinical relevance

摘要: This paper reviews the preclinical study of novel dopamine agonist pramipexole and its use in early Parkinson’s disease (PD). Emphasis will be given to those properties distinguishing this drug from other agonists, relevance data clinical trial results PD, putative neuroprotective compound. The conventional agonists are ergot-derived compounds that most widely used as adjunctive therapies advancing Examples bromocriptine pergolide. Pramipexole is an aminobenzothiazole compound, recently introduced for treatment both advanced PD. Its nonergot structure may reduce risk side-effects, considered unique ergot drugs, such membranous fibrosis. a full with high selectivity D2 receptor family. family includes D2, D3 D4 subtypes. has 5- 7-fold greater affinity subtype lower affinities The only minimal α2-adrenoceptor activity virtually no agonism or antagonism. optimal activation safe effective PD not known. Findings animal models studies indicate postsynaptic provides robust symptomatic improvement PD. Given pharmacological profile, it surprising was found ameliorating parkinsonian signs models. therapeutic effect been confirmed trials In disease, clear reduction chief motor manifestations improved activities daily living. Perhaps striking large number patients who have remained on monotherapy many months. majority these subjects maintained excess 24 months without requiring additional levodopa. contrast general experience older agonists. also favourable pharmacokinetic profile. It rapidly absorbed peak levels appearing bloodstream within 2 h oral dosing. absolute bioavailability > 90% can administered regard meals. significant effects antiparkinson drugs levodopa selegiline. excretion primarily renal and, thus, little impact hepatic cytochrome P450 enzymes related metabolic pathways. Pramipexole theorized ‘neuroprotectant’ properties. Oxyradical generation posited cause accelerant brain nigral cell death stimulates autoreceptors reduces synthesis turnover which minimize oxidative stress due metabolism. Furthermore, compound low oxidation potential serve oxyradical scavenger brain. In summary, new medication characteristics