Introduction. As the modification of the structure of existing medications is a productive way of the search of neuropsychotropic substances allowing to increase their effectiveness and safety [1, 2, 10], we have worked out several salts and compositions of baclophen (a GABA derivative - (4-amino-3-(para-chlorophenil)- butyric acid) with organic acids: citric, succinic, malic, oxalic, nicotinic, glutaminic and glycine. Neuroprotective action is typical of the GABA derivatives. Many structural analogues and derivatives of GABA possess neuroprotective activity – phenotropil, phenibut, pikamilon, and others [3, 8, 9]. The combination of baclophen and metabolically active acids was supposed to allow the creation of substances with marked neuroprotective effect.
Materials. Screening among 10 baclophen derivatives was performed on male Wistar rats. We used the model of brain ischemia produced by gravitational overload in craniocaudal vector in combination with the estimation of the degree of neurological deficit on the McGrow scale [6, 7], the model of electroconvulsive brain injury with maximal electroshock with the estimation of the duration of coma, time of restoration of spontaneous motion activity [4, 5] and the degree of amnesia of conditional reflex of passive avoidance, produced before maximal electroshock [1]. Baclophen, its derivatives and the comparison medications – pyracetam, phenibut, phenotropil were injected intraperitoneally in the equimolar concentrations one time 30 minutes before the modeling of neuropathology. Check rats received physiologic saline in the equivalent volume. Statistical processing of results: Cruscal-Wallace analysis, the Dunn criterion.
Results. Baclophen and its derivatives displayed neuroprotective and nootropic effect: decreased the degree of neurological deficit with the model of brain ischemia produced by gravitational overload in craniocaudal vector, reduced the duration of coma and time of restoration of spontaneous motion activity, prevent the amnesia of conditional reflex of passive avoidance on the maximal electroshock model. Glutamate-, glycine- and citrate comprising analogs of baclofen are statistically significantly more active than the initial substance. The majority of substances exceeded pyracetam, phenibut and RGPU-184 - even phenotropil by effectiveness.
Conclusion. The conducted stidies point at effectiveness of the creation of effective neuroprotectors on the basis of baclophen derivatives. Baclofen citrate excels baclofen in activity, all its’ examined derivatives, and the comparison medications – pyracetam, phenibut, phenotropil and is considered to be perspective for studying in the capacity of neuroprotector.
The work is submitted to the International Scientific Conference "Issues of science and education", Moscow, May 20-23, 2014, came to the editorial office оn 20.04.2014