Effects of (±)-idazoxan alone and in combination with L-DOPA methyl ester in MPTP-induced hemiparkinsonian monkeys

The effects of a combination of the alpha(2)-adrenergic receptor antagonist (+/-)-idazoxan with L-DOPA methyl ester were examined in three of four female adult monkeys ( Macaca nemestrina) rendered hemiparkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). (+/-)-Idazoxan (0.16, 0.63, and 1.0 mg/kg) was given i.m. 10 min before L-DOPA methylester (12.5 mg/kg). (+/-)-Idazoxan reduced the maximum peak of contralateral circling elicited during the first hour following injection of L-DOPA methyl ester, but prolonged the duration of the circling response up to 50% (p< 0.05). The data support a role for alpha(2)-adrenergic receptor mechanisms in modulating the effects of L-DOPA on nigrostriatal dopamine function in the MPTP monkey model of hemiparkinsonism.