Effect of dipeptide neurotensin analog dilept on extracellular concentrations of glutamate, GABA and HVA in N. accumbens of rat brain

The influence of dilept (GZR-123, N-caproyl-L-prolyl-L-tyrosine methyl ester)--a dipeptide analog of neurotensin (NT)--on extracellular concentration of glutamate, gamma-aminobutyric acid (GABA) and homovanillic acid (HVA) in n. accumbens of Wistar rats has been studied. By means of microdialysis, it was shown that dilept increases the concentrations of glutamate and GABA and decreases the HVA content in n. accumbens. These effects of dilept are similar to those produced by NT introduced into n. accumbens. Thus, dilept can be considered as a systemically active dipeptide analog of NT, which is capable of modulating the dysbalance of glutamate-, GABA-, and dopaminergic systems of n. accumbens. These neurochemical data taken together with previously established behavioral effects of dilept suggest that this dipeptide is a potential antipsychotic drug.     

Neurochemichal aspects of the pharmacological effect of 2,3,4-trimethoxy-<Emphasis Type="Italic">N</Emphasis>’-(8-methyl-8-azabicyclo[3.2.1.] octan-3-ylidene) benzohydrazide hydrochloride (LK-933)

The objective of this study was to investigate the effects of 2,3,4-trimethoxy-N'-(8-metyl-8-azabicyclo[3.2.1.] octan-3-ylidene) benzohydrazide hydrochloride (LK-933), a compound of the tropane group with anxiolytic and antimigraine activity, on the levels of monoamines and their metabolites in different brain structures of outbred mice using HPLC–ED. Administration of LK-933 caused an increase in the composite characteristics that describe the rate of dopamine transformation into its metabolites dioxyphenylacetic acid and homovanillic acid in the frontal cortex by 114 and 181%, respectively. The levels of homovanillic acid in the same structure increased by 49%. These data implicate the dopaminergic pathway in the mechanism of LK-933 action.