Motor effects of a dopamine stabilizer (GMC1111) in primate models of Parkinson and hemiparkinsonism - PubMed (original) (raw)

Motor effects of a dopamine stabilizer (GMC1111) in primate models of Parkinson and hemiparkinsonism

Rebecka Klintenberg et al. Eur J Pharmacol. 2003.

Abstract

The effects on motor behavior of a new potential dopamine stabilizer: 2-amino-6-(N,N-di-n-propylamino)thiazolo[4,5-f]indan (GMC1111) were investigated in common marmosets with 6-hydroxydopamine lesions within the median forebrain bundle (12 unilateral, 6 bilateral). GMC1111 was administered orally or subcutaneously (s.c.) to unilaterally 6-hydroxydopamine lesioned monkeys, either alone or together with s.c. injections of apomorphine (0.2 mg/kg) and the effect on rotational behavior was examined. GMC1111 (0.03-3.0 mg/kg) alone, orally or s.c., did not induce rotational behavior. When apomorphine and GMC1111 were injected simultaneously, rotations were nearly abolished in three monkeys with a baseline apomorphine-induced rotation rate below 13/min, whereas GMC1111 did not modify the rotations in three high-rotating animals (>17/min). Oral administration of GMC1111 (1.0 and 3.0 mg/kg) abolished the apomorphine-induced rotations in another six unilaterally dopamine-denervated monkeys, indicating a good oral bioavailability. A low dose of GMC1111 (0.3 mg/kg) administered s.c. to marmosets with bilateral nigrostriatal lesions produced a reduction of Parkinson symptoms of approximately the same degree as with levodopa/benserazide (15/3.75 mg/kg), while higher doses of GMC1111 were less effective. When levodopa/benserazide was administered together with various doses of GMC1111 (0.3-3.0 mg/kg), the levodopa-induced peak-dose dyskinesias were reduced with the highest dose of GMC1111 (3 mg/kg). Taken together, GMC1111 modifies dopaminergic activity in a normalizing direction. Parkinson symptoms, as well as levodopa-induced dyskinesias are both reduced. This suggests the arrival of another member of the new dopamine stabilizer family.

PubMed Disclaimer

Cited by

Alternative mitochondrial electron transfer as a novel strategy for neuroprotection.
Wen Y, Li W, Poteet EC, Xie L, Tan C, Yan LJ, Ju X, Liu R, Qian H, Marvin MA, Goldberg MS, She H, Mao Z, Simpkins JW, Yang SH. Wen Y, et al. J Biol Chem. 2011 May 6;286(18):16504-15. doi: 10.1074/jbc.M110.208447. Epub 2011 Mar 18. J Biol Chem. 2011. PMID: 21454572 Free PMC article.

Motor effects of a dopamine stabilizer (GMC1111) in primate models of Parkinson and hemiparkinsonism - PubMed (original) (raw)