Articles: gaba-modulators-pharmacology.
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Gamma-aminobutyric acid type A (GABAA) receptors provide the main inhibitory control in the brain. Their heterogeneity may make it possible to precisely target drug effects to selected neuronal populations. In situ hybridization using rat brain sections has revealed a unique expression of GABAA receptor epsilon and theta subunit transcripts in the locus coeruleus, where they are accompanied at least by alpha3, alpha2, beta1 and beta3 subunits. Here, we studied the pharmacology of the human alpha3beta1, alpha3beta1epsilon, alpha3beta1theta and alpha3beta1epsilontheta receptor subtypes expressed in Xenopus oocytes and compared them with the gamma2 subunit-containing receptors. ⋯ The epsilon and theta subunits bring additional features to alpha3beta1 GABAA receptors. These receptor subtypes may constitute as novel drug targets in selected brain regions, e.g., in the brainstem locus coeruleus nuclei.
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Randomized Controlled Trial Comparative Study Clinical Trial
A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers.
Pregabalin potently and selectively binds to the alpha(2)-delta subunit of voltage-dependent calcium channels, reducing calcium influx and modulating release of downstream excitatory neurotransmitters, such as glutamate. Pregabalin has demonstrated robust efficacy for several disease states, but its neuropharmacology is still being elucidated. ⋯ Pregabalin did not differ on most assessments from placebo, producing only minor, transient impairment on some objective cognitive and psychomotor measures, suggesting a relatively benign CNS side-effect profile.
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Comparative Study
Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate is a novel positive modulator of GABAA receptors.
Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABA(A) receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. ⋯ This drug induced a reversible loss of the righting reflex in Xenopus tadpoles and it elicited hypnosis (5 mg/kg) after intravenous administration in rats. These results indicate that the pharmacological profile of TG41 is similar to that of general anesthetics which potentiate the activity of GABA(A) receptors containing the beta2 or beta3 subunit.
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Journal of anesthesia · Jan 2005
Randomized Controlled Trial Clinical TrialEffect of flumazenil on recovery from sevoflurane anesthesia in children premedicated with oral midazolam before undergoing herniorrhaphy with or without caudal analgesia.
Oral midazolam is frequently used to treat children, but its effect on recovery from anesthesia is controversial. This study was designed to evaluate the effect of flumazenil on reversal of midazolam during recovery from sevoflurane-induced anesthesia in children who underwent caudal analgesia compared to those who did not. ⋯ Caudal analgesia and avoiding the use of flumazenil synergistically resulted in the emergence from anesthesia in a less agitated state for children who underwent herniorrhaphy after oral midazolam premedication.
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Substance use & misuse · Jan 2005
ReviewA brief overview of the clinical pharmacology of "club drugs".
Four different "club drugs" are reviewed: MDMA (methylenedioxymethamphetamine, "Ecstasy"), GHB (gamma-hydroxybutyrate), ketamine, and Rohypnol (flunitrazepam). The neurobiology, clinical pharmacology, and treatment issues for each are discussed.