Evaluation of the anticonvulsant profile of progesterone in male amygdala-kindled rats. 1998

S Mohammad, and A Abolhassan, and M H Pourgholami
Department of Pharmacology, Faculty of Medicine, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

While there is clinical evidence that progesterone has anticonvulsant activity in women with complex partial seizures, previous studies on the anticonvulsant effect of progesterone in experimental animal models are inconclusive. Moreover, the effect of progesterone on seizure parameters in fully amygdala-kindled rats which best resemble complex partial seizures has not been evaluated. Therefore, in the present work the anticonvulsant effect of progesterone at doses of 10, 30, 60 and 75 mg/kg in fully amygdala-kindled male rats was studied. Only at the high and sedative dose of 75 mg/kg, progesterone suppressed behavioral seizures and afterdischarges elicited 10 min after intraperitoneal (i.p.) administration. Pretreatment with the progesterone antagonist, 17beta-hydroxy-11beta-(4-dimethylaminophenyl)-17alpha-(prop- 1-ynyl)-estra-4,9-dien-3-one (RU 38486) at the dose of 3 mg/kg did not inhibit the anticonvulsant activity of progesterone, while pretreatment with the GABA(A) receptor antagonist, bicuculline (2 mg/kg) blocked the anticonvulsant effect of progesterone. Neither RU 38486 nor bicuculline had any effect on the seizure parameters. These findings suggest that only at large and sedative doses, progesterone has some anticonvulsant activity in male amygdala-kindled rats which may be partly mediated via the GABA(A) receptor complex interaction.

UI MeSH Term Description Entries
D006993 Hypnotics and Sedatives Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. Hypnotic,Sedative,Sedative and Hypnotic,Sedatives,Hypnotic Effect,Hypnotic Effects,Hypnotics,Sedative Effect,Sedative Effects,Sedatives and Hypnotics,Effect, Hypnotic,Effect, Sedative,Effects, Hypnotic,Effects, Sedative,Hypnotic and Sedative
D007696 Kindling, Neurologic The repeated weak excitation of brain structures, that progressively increases sensitivity to the same stimulation. Over time, this can lower the threshold required to trigger seizures. Kindlings, Neurologic,Neurologic Kindling,Neurologic Kindlings
D008297 Male Males
D011374 Progesterone The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS. Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D003292 Convulsants Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. Convulsant,Convulsant Effect,Convulsant Effects,Effect, Convulsant,Effects, Convulsant
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006727 Hormone Antagonists Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites. Antagonists, Hormone
D000679 Amygdala Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system. Amygdaloid Body,Amygdaloid Nuclear Complex,Amygdaloid Nucleus,Archistriatum,Corpus Amygdaloideum,Intercalated Amygdaloid Nuclei,Massa Intercalata,Nucleus Amygdalae,Amygdalae, Nucleus,Amygdaloid Bodies,Amygdaloid Nuclear Complices,Amygdaloid Nuclei, Intercalated,Amygdaloid Nucleus, Intercalated,Amygdaloideum, Corpus,Amygdaloideums, Corpus,Archistriatums,Complex, Amygdaloid Nuclear,Complices, Amygdaloid Nuclear,Corpus Amygdaloideums,Intercalata, Massa,Intercalatas, Massa,Intercalated Amygdaloid Nucleus,Massa Intercalatas,Nuclear Complex, Amygdaloid,Nuclear Complices, Amygdaloid,Nuclei, Intercalated Amygdaloid,Nucleus, Amygdaloid,Nucleus, Intercalated Amygdaloid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic

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