Biomedical subjects
Publications and source records attributed to G S Kozlova.
We studied mutagenic, embryotoxic, and teratogenic properties of calcium ketopantoyl aminobutyrate, a preparation proposed as a new drug. Long-term oral administration of calcium ketopantoyl aminobutyrate produced no mutagenic, embryotoxic, and teratogenic effects.
We studied the allergic and immunotoxic effects of a new promising medicinal preparation calcium ketopantoyl aminobutyrate. Calcium ketopantoyl aminobutyrate produced no negative effects on general mechanisms of humoral and cellular immunity. This preparation did not modulate the anaphylactic reaction to bovine serum, exhibited no mitostatic and lymphotoxic properties, had no effect on the delayed-type hypersensitivity response, and did not produce active cutaneous anaphylactic reaction.
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The investigation of toxicity of calcium ketopantoylaminobutyrate (Ca-KPAB) showed that this newly synthesized compound belongs to the class of low-toxicity substances. The LD 50 of Ca-KPAB for oral administration is lower than that of pantogam. No toxicity manifestations and local irritant activity was observed upon chronic administration of Ca-KPAB. The therapeutic index of Ca-KPAB is more than 17 times that of pantogam.
Comparative study of the sedative (calming) properties of the new drug calcium ketopantoylaminobutyrate (Ca-KPAB) and the reference drug pantogam (calcium homopantotenate) showed that the newly synthesized compound produces a more pronounced calming action in several standard neuropharmacological tests (spontaneous motor activity, barbiturate antagonist, etc.) and exhibits some additional advantages. Thus, a slight modification of the chemical structure made possible a significant reduction in the effective drug dose.
Experimental investigation of calcium ketopantoylaminobutyrate (Ca-KPAB), a new drug with a structure close to that of pantogam, showed that Ca-KPAB exhibits a pronounced antihypoxant effect on the normobaric and histotoxic hypoxia models. The new drug also produced a more pronounced antiamnesic action as compared to that of pantogam. A significant decrease in the effective drug dose in the case of Ca-KPAB is explained by its ability to readily bypass the blood - brain barrier.
The cardiovascular system was examined in acute, subacute and chronic intoxications with nitroglycerin. It was revealed that morphofunctional alterations were uniform in nature, being more demonstrable in chronic exposure during 6 months. Myocardial alterations were characterized by disturbed hemodynamics, dystrophy, focal myocarditis, changes in the activity of enzymes, and changes in the electrocardio- and rheovasographic readings. Prolonged intoxication produced more profound and stable alterations.
The permeability through the blood-brain barrier of N-(4-hydroxy-3,3 dimethyl-2-oxo-1-butiryl) gamma-aminobutyric acid calcium salt, a new neurotropic drug calcium ketohomopantothenate (KPA-Ca), was studied in comparison with that of calcium homopantothenate, pantogam (P) Liquid chromatography analysis showed that after oral administration of KPA-Ca and P both forms of these agents, namely, oxy- and keto- derivatives of homopantothenic acid, were found in the brain of experimental rats, the KPA-Ca (ketoform) content being higher. Pharmacological studies showed that KPA-Ca penetrates the blood-brain barrier in greater amounts and causes a higher effect on the rate of cerebral blood flow when it is administered per os in a dose of 50 mg/kg.
The authors studied the permeability of the blood-brain barrier (CEB) to two nootropics: calcium ketogomopantothenate (KRA-Ca), a GABA derivative, and and calcium salt of oxybutyrate (OB-Ca), a derivative of GOBA. It was established that both preparations penetrate the CEB easily and are found in the brain at different intervals after their administration. However, essential differences in the distribution constant of these drugs were disclosed: KPA-Ca permeated the CEB more intensively and was accumulated in larger amounts in the late-term intervals.