Subject(s)
Comparative Study , Guinea Pigs , Rats , Histamine Antagonists , Basic Homeopathic Research , Bees , Cimetidine , HistamineABSTRACT
4,4-Dimethyl-1-[3,4-(methylenedioxy)-phenyl]-1-penten-3-ol (stiripentol), selected from a series of alpha-ethylene alcohols, demonstrated anticonvulsant activity in studies in the rat and rabbit in which convulsions were induced electrically and chemically using pentetrazol, bicuculline and strychnine. Neurochemical studies showed that stiripentol in vitro did not act as a GABA receptor agonist, instead it inhibited the synaptosomal uptake of 3H-labelled GABA. Stiripentol has been shown elsewhere to inhibit GABA transaminase. These findings suggest that the anticonvulsant activity of stiripentol involves two aspects of the GABAergic mechanism in which the metabolic transamination and synaptosomal uptake of this neurotransmitter are inhibited.
Subject(s)
Anticonvulsants , Brain Chemistry/drug effects , Dioxolanes/pharmacology , Dioxoles/pharmacology , Animals , Dioxolanes/metabolism , Dioxolanes/toxicity , Electroshock , In Vitro Techniques , Male , Mice , Rats , Rats, Inbred Strains , Receptors, Cell Surface/drug effects , Receptors, Cell Surface/metabolism , Receptors, GABA-A , Receptors, Glycine , Synaptosomes/metabolism , gamma-Aminobutyric Acid/metabolismABSTRACT
Intracerebroventricular (i.c.v.) injections of AR-C 239 (30 micrograms/kg), a selective alpha 1-adrenoceptor blocking drug, did not modify the heart rate in normotensive control (without pretreatment), bilaterally vagotomized and beta blocked rats and in spontaneously hypertensive (SH) bilaterally vagotomized rats. Intracisternal (i.c.) administrations of AR-C 239 (30 micrograms/kg) however decreased the heart rate in normotensive beta blocked and in SH bilaterally vagotomized rats. The differential effect on heart rate of i.c.v. versus i.c. administration of AR-C 239 suggests a brainstem localization of the alpha 1-adrenoceptors involved. The binding of [3H]prazosin was significantly higher in homogenates from whole brain and in membranes from the cerebral cortex and hypothalamus of SH rats as compared to normotensive rats. In addition, the binding of [125I]BE 2254, a new iodinated radioligand of high specific radioactivity used to characterize alpha 1-adrenoceptors, was significantly increased in membranes from the NTS of SH rats. These results suggest that central alpha 1-adrenoceptors localized in the brainstem and in the hypothalamus and the cortex play a role in the control of vagal tone in normotensive rats and of sympathetic activity in SH animals. Thus, it is postulated that central alpha 1-adrenoceptors may participate in either the genesis or the maintenance of genetic hypertension.
