[Fenibut and fenazepam as potential protectors of pregnancy with a GABA-ergic mechanism of action]. / Fenibut i fenazepam kakpotentsial'nye gravidoprotektory GAMKergicheskogo mekhanizma deistviia.

It has been shown that the GABAergic system of the myometrium takes part in regulation of uterine contractility during the development of pregnancy Fenibut and phenazepam exhibit a specific uterotropic effect. The uterodepressant effect of fenibut is realized via the inhibiting GABA-receptors of the myometrium. The uteroinhibiting effect of phenazepam is mediated through the interaction with the postsynaptic GABA-benzodiazepin-C1-receptor complex of the myometrium.

[The GABA-ergic system of the myometrium: a basis for the clinical study of GABA-positive substances as pregnancy protectors]. / GAMKergicheskaia sistema miometriia: obosnovanie k klinicheskomu izucheniiu GAMK-polozhitel'nykh veshchestv v kachestve gravidoprotektorov.

Radioligand method was used to show 14C-GABA, 3H-flunitrazepam binding sites in human, rat, rabbit myometrium. We have used muscimol, bicucullin, picrotoxin, baclofen, thiosemicarbazide for identification of GABA-benzodiazepine receptor complexes and in pharmacologic analysis of uterine contractility. Receptor affinity depended on pregnancy term (early or late). A conclusion is drawn that GABAA, GABAB, and benzodiazepine receptors of the peripheral nervous system mediate the inhibitory effect of GABA-positive substances on mammalian uterine contractility.

[Action of GABA-positive preparations on uterus-stimulating effects of activating neuromediators, prostaglandin F2 alpha and oxytocin]. / Vliianie GAMK-pozitivnykh veshchestv na uterostimuliruiushchie éffekty vozbuzhdaiushchikh neiromediatorov, prostaglandina F2alfa i oksitotsina.

Experiments on isolated strips of the non-pregnant rabbit and rat uterus showed the ability of dopamine, noradrenaline, serotonin, acetylcholine, prostaglandin F2 alpha, oxytocin to increase the uterine strips contractile activity. On the other hand, GABA, GABAB receptors agonist phenibut and diazepam inhibit the stimulating effects of the above mentioned substances, thus showing the properties of physiological antagonists of these neuromediators, prostaglandin and oxytocin.

[The participation of the GABA-A and GABA-B receptors in the mechanism of the inhibition of the contractile activity in the rabbit myometrium under the influence of GABA, AOAA and fenibut]. / Uchastie GAMK-A- i GAMK-B-retseptorov v mekhanizme tormozheniia sokratitel'noi aktivnosti miometriia krolikov pod vliianiem GAMK, AOUK i fenibuta.

Experiments on isolated strips of the rabbit uterus showed the stimulating effects of small doses of GABA, AOAA and phenibut on uterine contractility, while large doses exerted the reverse (suppressing) effects. Administration of bicuculline and picrotoxin before or after the above-mentioned drugs reduced their suppressing effects on uterine muscle contractility. The data postulate the involvement of GABAA and GABAB receptors in the drugs action on the rabbit uterus.

[Study of the GABA-benzodiazepine receptor system of the human myometrium]. / Issledovanie GAMK-benzodiazepinovykh retseptornykh sistem miometriia cheloveka.

A specific [3H] GABA and [14C] flunitrazepam binding sites have been identified in a membrane fraction of human myometrium. The specific binding of [14C] GABA was displaced by unlabelled GABA and bicuculline. It was shown that the binding of [3H] flunitrazepam to membrane preparations is enhanced in the presence of GABA. A similar reciprocal effect of benzodiazepines to enhance [14C] GABA binding has been demonstrated. The present results indicate that GABAA-BD receptors complexes may have a functional significance in human ovary.

[Effect of fenibut and seduxen on fetal development in the second half of pregnancy]. / Issledovanie vliianiia fenibuta i seduksena na razvitie ploda vo vtoroi polovine beremennosti.

In experiments on rats it was found that fenibut (50 mg/kg, 1/20 of LD50) during a single and repeated administration in the fetus period of pregnancy does not exert any negative effect on the maternal organism, the growth and development of the fetus. Seduxen administered in a dose of 50 mg/kg (1/80 of LD50) alone and in combination with fenibut was shown to decrease the female body weight gain and to disturb the fetus development. Following a single administration on the 17th day of pregnancy, the effect was poorly pronounced.

[Effect of gamma-aminobutyric acid and its agonists on uterine contractile activity]. / Vliianie gamma-aminomaslianoi kisloty i ee agonistov na sokratitel'nuiu aktivnosti matki.

In chronic experiments on female rabbits it was shown that GABA-receptor agonist phenibut given in small doses exerts the stimulating effect, while GABA and phenibut administered in large doses suppress the uterine contractile activity, acting probably as modulators of presynaptic release of neuromediators. Diazepam displays the regulatory effect on the uterine contractions via the postsynaptic receptor mechanisms. The data suggest the involvement of the GABAergic mechanisms in the uterine contractile function.

[Effect of gamma-aminobutyric acid, its agonists and antagonists on uterine smooth muscle]. / Vliianie gamma-aminomaslianoi kisloty, ee agonistov i antagonistov na gladkuiu muskulaturu matki.

Experiments on isolated strips of the rabbit uterus showed the ability of GABA, GABAA-receptor agonist (diazepam) and GABAB-receptor antagonist (phenibut) to inhibit uterine contractility. GABAA-receptor antagonist (bicuculline) had a stimulating effect on contractility. It is assumed that GABA-ergic system plays an important role in the regulation of functional inhibition of contractile activity in the rabbit uterus, with GABA agonists regarded as potential gravidoprotectors in uterine hyperactivity or threatening miscarriage.

[Effect of sodium oxybutyrate on the development of uterine hyperactivity]. / Vliianie natriia oksibutirata na razvitie giperaktivnosti matki.

Chronic experiments on ovariectomized rabbits were made to study the effect of sodium hydroxybutyrate, a gamma-hydroxybutyric acid derivative, on the myometrium. The mechanical distension of the uterine horn provoked hyperactivity. The dopamine agonist levodopa dramatically potentiated the mechanical hyperactivity of the rabbit uterus. Sodium hydroxybutyrate (800 mg/kg i.v.) significantly inhibited the mechanical and levodopa uterine hyperactivity. The most powerful inhibitory action was produced on the levodopa hyperactivity. Sodium hydroxybutyrate can be regarded as a potential gravidoprotector. It may be assumed that the dopaminergic system is involved in the development of the myometrium hyperactivity. The GABA-ergic mechanisms are likely to play a definite role in the reduction of uterine contractility.

[Barohysterography in study of the action of pharmacological agents on the myometrium]. / Barogisterografiia v izuchenii deistviia na miometrii farmakologicheskikh sredstv.

A method was modified for implanting into the rabbit uterine horn lumen of a rubber balloon for recording fluctuations of the intrauterine pressure. Barohysterography and electrohysterography were compared as to the action of oxytocin on the uterine contractility. It was established that barohysterography is a more informative test in the assessment of the action of pharmacological agents on individual components of the motor-isometric activity of the uterus.