Inhibitory Effects of Talipexole and Pramipexole on MPTP-Induced Dopamine Reduction in the Striatum of C57BL/6N Mice.

Abstract

ABSTRACT-Wehave investigated the effects of two novel antiparkinsonian drugs, talipexole (Domin®) and pramipexole, on MPTP-induced dopamine (DA) reduction in the striatum of C57BL/6N mice in comparison with those of bromocriptine. Fifteen days after MPTP treatment (25 mg/kg, i.p., given daily for 5 days), the DA content in the striatum was decreased to 40-60010 of the control value. Among the three dopamine receptor agonists, talipexole and pramipexole (1 mg/kg, i.p., once a day for 20 days) more sig nificantly suppressed the MPTP-induced DA reduction in the striatum than bromocriptine (10 mg/kg, i.p., once a day for 20 days). Talipexole did not influence [3H]MPP+ uptake into striatal synaptosomes. These results suggest that talipexole and pramipexole have a protective effect against MPTP-induced DA reduc tion in the striatum of C57BL/6N mice.

Original article Neuroprotective effect of rotigotine against complex I inhibitors, MPP+ and rotenone, in primary mesencephalic cell culture

“…Some dopamine agonists have exhibited neuro protection for dopaminergic neurons against MPTP in mice, for example bromocriptine [19] and prami pexole [16]. Neuroprotection against MPP + in prima ry dopaminergic culture from embryonic mouse or rat mesencephalon was demonstrated for lisuride [11], and pramipexole and ropinirole, respectively [6].…”

Antiparkinsonian Drugs and Their Neuroprotective Effects.

“…), 25,55,56) and glial cell line-derived neurotrophic factor (GDNF). 57) In in vivo studies, MPTP-induced striatal DA neurodegeneration in C57BL/6 mouse and monkey and brain damage in other models were also inhibited by selegiline (deprenyl), 58,59) bromocriptine, 59,60) pergolide, 58) pramipexole, 59,61) talipexole, 59,62) immunophilin ligands (GIP-1046, FK-506, cyclosporin A) 63,64) and several neurotrophic factors (GDNF, neurotrophin-4/5, basic fibroblast growth factor, etc.). [65][66][67][68] In contrast, epidemiological studies have indicated that the incidence and prevalence of PD tend to be lower in women than men, 69) and in cigarette-smokers compared to nonsmokers.…”

Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists

“…DA agonists are also used for treatment of PD, some of which have been shown to be neuroprotective in Parkinson's models (Anderson et al f , 2001) and, perhaps, in PD itself (Marek et al, 2002). Antiparkinsonian agents that are direct DA agonists such as apomorphine (Grünblatt et al, 1999), bromocriptine (Muralikrishnan and Mohanakumar, 1998), and pramipexole (Kitamura et al, 1997), have been shown to be neuroprotective against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-(MPTP-) induced damage to the DA system in mice. MPTP administration to mice is considered a good model of studying neuroprotection because MPTP is known to produce parkinsonism in humans and in subhuman species through selective loss of DA-ergic neurons of the SN (Burns et al, 1983;Langston et al, 1983) There are a number of related compounds to 1983).…”