Antiparkinsonian Properties of a Nerve Growth Factor Dipeptide Mimetic GK-2 in in Vivo Experiments

Abstract

An intraperitoneal injection of GK-2 (dipeptide mimetic of nerve growth factor, 0.01-5.00 mg/kg) 24 h before the adverse exposure reduced the severity of haloperidol-induced catalepsy in rats. This agent retained the activity after oral administration in a dose of 10 mg/kg. An intraperitoneal injection of GK-2 in a dose of 1 mg/kg reduced the severity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian syndrome in mice. Administration of GK-2 45 min after haloperidol treatment was also followed by a decrease in the degree of catalepsy. The repeated intraperitoneal treatment with GK-2 in a dose of 1 mg/kg after intrastriatal injection of 6-hydroxydopamine was shown to prevent the development of apomorphine-induced rotations in rats.

Original Nerve Growth Factor Mimetic Dipeptide GK-2 Restores Impaired Cognitive Functions in Rat Models of Alzheimer’s Disease

“…The GK-2 doses (0.5 and 1 mg/kg) were selected as the ones most efficient in vivo according to the data obtained in a study of the dose-dependent effect of this compound in the haloperidol catalepsy model in rats used for screening compounds with potential antiparkinsonian activity [23]. The efficacy of these doses was also confirmed in various cerebral ischemia models [20-22].…”

“…GK-2 prevented H 2 O 2 - or glutamic-acid-induced destruction of immortalized mouse hippocampal neurons in culture (HT-22 line) and protected rat pheochromocytoma PC12 cells from the action of neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) [19]. Dipeptide GK-2 exhibited neuroprotective properties and improved cognitive functions [20-22], and reduced the severity of behavioral symptoms in a number of models of the parkinsonian syndrome [23] in experimental models of acute and chronic cerebral ischemia in rats. Dipeptide GK-2 exhibits low toxicity (LD 50 = 714 mg/kg upon intravenous administration to male mongrel mice) and shows none of the major side effects typical of NGF.…”

A Novel Dimeric Dipeptide Mimetic of the Nerve Growth Factor Exhibits Pharmacological Effects upon Systemic Administration and Has No Side Effects Accompanying the Neurotrophin Treatment

“…At the same time, marked contralateral rotations were observed in rats with striatal lesions. GK-2 almost completely abolished this turning behavior [16].…”

“…after MPTP (15 mg/kg, i.p. with 2 h intervals, to a total of 4 times) completely abolished rigidity in mice by the 14th post-lesion day [16].…”

“…and retains the activity after oral administration in a dose of 10 mg/kg. Experiments with various time regimes of GK-2 treatment (48, 24, 16, 1 h before and 30 and 45 min after the haloperidol injection) showed that this agent exhibits anticataleptic activity under the conditions of administration 24 h before or 45 min after the haloperidol injection [16].…”