RESUMO
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.
Assuntos
Ansiolíticos , Benzodiazepinas , Benzodiazepinonas/farmacologia , GABAérgicos/farmacologia , Prenhez/efeitos dos fármacos , Ácido gama-Aminobutírico/análogos & derivados , Animais , Diestro/efeitos dos fármacos , Feminino , Miométrio/efeitos dos fármacos , Ovariectomia , Gravidez , Coelhos , Ratos , Receptores de GABA-A/efeitos dos fármacos , Fatores de Tempo , Ácido gama-Aminobutírico/farmacologiaAssuntos
Receptores de GABA/efeitos dos fármacos , Receptores de GABA/fisiologia , Contração Uterina/efeitos dos fármacos , Contração Uterina/fisiologia , Animais , Tubas Uterinas/efeitos dos fármacos , Tubas Uterinas/fisiologia , Feminino , Humanos , Ovário/efeitos dos fármacos , Ovário/fisiologia , Placenta/efeitos dos fármacos , Placenta/fisiologia , GravidezAssuntos
Ameaça de Aborto/prevenção & controle , Ansiolíticos , Benzodiazepinas , Benzodiazepinonas/farmacologia , Contração Uterina/efeitos dos fármacos , Ácido gama-Aminobutírico/análogos & derivados , Ameaça de Aborto/fisiopatologia , Animais , Benzodiazepinonas/administração & dosagem , Combinação de Medicamentos , Feminino , Contração Isométrica/efeitos dos fármacos , Gravidez , Coelhos , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/farmacologiaRESUMO
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.
Assuntos
Miométrio/efeitos dos fármacos , Prenhez/efeitos dos fármacos , Receptores de GABA/efeitos dos fármacos , Animais , Diestro/efeitos dos fármacos , Feminino , Antagonistas GABAérgicos , Humanos , Técnicas In Vitro , Miométrio/química , Miométrio/fisiologia , Gravidez , Coelhos , Ensaio Radioligante , Ratos , Receptores de GABA/análise , Receptores de GABA/fisiologia , Contração Uterina/efeitos dos fármacosRESUMO
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.
Assuntos
Dinoprosta/farmacologia , Ocitocina/farmacologia , Contração Uterina/efeitos dos fármacos , Ácido gama-Aminobutírico/farmacologia , Animais , Anticonvulsivantes/farmacologia , Diazepam/farmacologia , Dinoprosta/antagonistas & inibidores , Eletromiografia , Feminino , Técnicas In Vitro , Ocitocina/antagonistas & inibidores , Coelhos , Ratos , Ácido gama-Aminobutírico/análogos & derivadosAssuntos
Ameaça de Aborto/prevenção & controle , Diazepam/administração & dosagem , Modelos Animais de Doenças , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Tranquilizantes/administração & dosagem , Ácido gama-Aminobutírico/análogos & derivados , Animais , Relação Dose-Resposta a Droga , Desenvolvimento Embrionário e Fetal/fisiologia , Feminino , Idade Gestacional , Gravidez , Ratos , Ácido gama-Aminobutírico/administração & dosagemRESUMO
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.
Assuntos
Ácido Amino-Oxiacético/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Contração Uterina/efeitos dos fármacos , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/farmacologia , Animais , Bicuculina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Técnicas In Vitro , Picrotoxina/farmacologia , Coelhos , Receptores de GABA-A/fisiologia , Contração Uterina/fisiologiaRESUMO
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.
Assuntos
Miométrio/química , Receptores de GABA-A/análise , Sítios de Ligação , Radioisótopos de Carbono , Feminino , Flunitrazepam/metabolismo , Humanos , Miométrio/metabolismo , Receptores de GABA-A/metabolismo , TrítioRESUMO
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.
Assuntos
Diazepam/efeitos adversos , Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Prenhez/efeitos dos fármacos , Tranquilizantes/efeitos adversos , Ácido gama-Aminobutírico/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Idade Gestacional , Osteogênese/efeitos dos fármacos , Gravidez , Ratos , Ácido gama-Aminobutírico/efeitos adversosRESUMO
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.
Assuntos
Contração Uterina/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Animais , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Feminino , Coelhos , Fatores de Tempo , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/farmacologiaRESUMO
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.
Assuntos
Diazepam/farmacologia , Músculo Liso/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/farmacologia , Animais , Bicuculina/farmacologia , Convulsivantes/farmacologia , Feminino , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Coelhos , Útero/efeitos dos fármacosRESUMO
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.
Assuntos
Hidroxibutiratos/farmacologia , Oxibato de Sódio/farmacologia , Contração Uterina/efeitos dos fármacos , Animais , Castração , Depressão Química , Feminino , Levodopa/farmacologia , Tono Muscular/efeitos dos fármacos , CoelhosRESUMO
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.