Synthesis and antioxidant activity evaluation of novel antiparkinsonian agents, aminoadamantane derivatives of nitroxyl free radical.

Two new analogues of the antiparkinsonian drug 1-aminoadamantane: 4-(1-adamantylamino)-2,2,6,6-tetramethylpiperidine-1-oxyl and 4-(1-adamantylammonio)-1-hydroxy-2,2,6,6-tetramethylpiperidinium dihydrochloride have been synthesized. Their antioxidant activity towards reactive oxygen species (ROS: (z.rad;)OH and O(2)(z.rad;-)) have been evaluated in three test systems. The compound with nitroxide substituent displays higher anti-oxidative capacity than those containing hydroxylamine. The in vivo study of ROS-involving 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-rat model of induced parkinsonism was undertaken to ascertain the neuroprotective ability of the novel synthesized compounds-antioxidants. The data clearly shows that the nitroxide free radical moiety of the molecule is necessary for their neuroprotective action on dopaminergic neurons under the applied conditions of deep oxidative stress caused by the neurotoxin (MPTP). The new synthesized analogues may find application in treatment of parkinsonian syndromes, either to block or to reduce the ROS-mediated neuronal damage and death.