Mechanism of Action of Phosphorylacetic Acid Hydrazides as Memory Enhancers and Neuroptotectors

Comparative study of the structure and biological activity of potential psychotropic drugs phosenazid and CAPAH

“…Thus, the spectrum of psychotropic activity of the two phosphorylacetic acid hydrazides under consideration is determined both by the presence of arylphosphoryl and hydrazide fragments (as was demonstrated previously [5,19] and by features in the chemical, spatial, and electron structure of their molecules. In particular, the presence of a polar ester bond P 1 -O 3 in molecule I probably accounts for a broader spectrum of psychotropic activity demonstrated by CAPAH.…”

“…Previously, we demonstrated that the manifestations of a psychotropic activity in the series of nitrogen-containing derivatives of phosphorylacetic acid depends on the presence of both phosphoryl and hydrazide moieties, the maximum activity being inherent in unsubstituted phosphorylacetic acid hydrazines [5,11]. Investigation of the neuropharmacological properties of hydrazides I and II showed that, along with the general pattern of psychotropic action, these compounds differ in the manifestation of particular effects.…”

“…Of special interest are phosphorylacetic acid hydrazides and their derivatives, which have been extensively studied in recent years. These compounds exhibit an original combination of properties, producing a complex action upon the CNS while being free of anticholinesterase activity [4,5]. Potential psychotropic drugs selected from this class of substances include 2-[4-(dimethylamino)phenyl]-(2-chloroethoxy)-phosphorylacetic acid hydrazide (I, CAPAH) and (2-diphenylphosphoryl)acetic acid hydrazide (II, phosenazid).…”

Stereoselective synthesis and neurotropic activity of phosphorylacetic acid derivatives

“…These compounds belong to the new class of neuroactive compounds -phosphorylacetic acid hydrazides, which exhibit an original combination of affects upon the CNS while being free of anticholinesterase activity [1,2]. In particular, CAPAH produces an antidepressant action and, in addition, improves memory and increases learning ability [3].…”