Different effects of α- and γ-polymorphs of glycine on behavior of GC rats predisposed to catalepsy

Abstract

1 The amino acid glycine is currently widely used in medicine. Medicines containing glycine can reduce the psychoemotional stress and aggression, raise social adaptation, normalize sleep and enhance mental per� formance, reduce the severity of brain disorders in ischemic stroke, and reduce the toxic effect of alcohol [1–3]. In the United States, drugs containing glycine have been approved for the treatment of negative symptoms in patients with schizophrenia [4]. Usually glycine is administrated as sublingual pills. It was found that the solution of glycine is less effective than the dry form [5]. Hence we can assume that the biolog� ical activity of glycine is associated not only with its chemical formula per se, but with the characteristics of the solid, such as its crystal structure (polymorphs). When glycine is used in formulations, its activity may also depend on the structure and properties of supramolecular complexes with excipients. Despite the fact that glycine can exist as several polymorphs [6], the influence of the crystal structure on the biolog� ical activity was not investigated. Neither catalogs nor packages of reagents and drugs containing glycine (as a pure substance or as a part of multicomponent pills) provide information on which polymorph(s) of glycine are present in the sample. In the publications devoted to the therapeutic use of glycine, there is no informa� 1 The article was translated by the authors. tion on which polymorph(s) of glycine have been used. 2 The aim of this work was to compare the effect of α and γ polymorphs of glycine on behavior of GK rats with a genetic predisposition to catalepsy. As a result, it was shown that γ�polymorph of glycine has a higher biological activity than the α�form. This effect was very unusual because both forms of glycine have almost the same kinetics of dissolution and their mol� ecules have the same conformation. An interpretation of the difference in the biological activity of two poly� morphs of glycine can be sought in the different struc� tures of molecular associates that enter the body when the two forms of drug have been taken orally. Glycine bought from Soyuzkhimreaktiv (Russia) contained a mixture of α and γ polymorphs; it was recrystallized to obtain pure α and γ polymorphs. The