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Structural Analogs of the GABAkine KRM-II-81 Are Orally Bioavailable Anticonvulsants without Sedation.
J Pharmacol Exp Ther
April 2023
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin (K.P.P., F.R., L.K.G., N.M.Z., M.J.M., L.A.A., D.S., M.Y.M., V.V.N.P.B.T., J.M.C., J.M.W.);
To provide back-up compounds to support the development of the GABA receptor (GABAAR) potentiator KRM-II-81, three novel analogs were designed: replacing the pyridinyl with 2'-Cl-phenyl (FR-II-60), changing the positions of the N and O atoms in the oxazole ring with addition of an ethyl group (KPP-III-34 and KPP-III-51), or substituting a Br atom for the ethynyl of KRM-II-81 (KPP-III-34). The compounds bound to brain GABAARs. Intraperitoneal administration of FR-II-60 and KPP-III-34 produced anticonvulsant activity in mice [maximal electroshock (MES)-induced seizures or 6 Hz-induced seizures], whereas KPP-III-51 did not.
View Article and Find Full Text PDFEthopharmacological analysis of the open elevated plus-maze in mice.
Behav Brain Res
June 2013
Laboratory of Pharmacology, School of Pharmaceutical Sciences, University of Estadual Paulista, Araraquara, SP, Brazil.
Exposure of rodents to an open elevated plus-maze (oEPM) elicits antinociception and increases plasma corticosterone levels. However, no studies have yet assessed the defensive behaviour repertoire of animals in this modified test. In Experiment 1, factor analysis was employed to characterise the behavioural profile of mice exposed to the oEPM.
View Article and Find Full Text PDFEpileptiform response of CA1 neurones to convulsant stimulation by cyclothiazide, kainic acid and pentylenetetrazol in anaesthetized rats.
Seizure
May 2011
Institutes of Brain Science, State Key Laboratory for Medical Neurobiology, Fudan University, Shanghai 200032, China.
We have previously reported that cyclothiazide (CTZ) evokes epileptiform activities in hippocampal neurons and induces seizure behavior. Here we further studied in vivo the sensitivity of the hippocampal CA1 neurons in response to CTZ in epileptogenesis in comparison with two other classic convulsants of kainic acid (KA) and pentylenetetrazol (PTZ). CTZ administered intracerebral ventricle (i.
View Article and Find Full Text PDFMeasuring anxiety- and locomotion-related behaviours in mice: a new way of using old tests.
Psychopharmacology (Berl)
July 2010
Psychology Department and Neuroscience Institute, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 4J1.
Rationale: Batteries of tests that are thought to measure different aspects of anxiety-related behaviour are used to characterise mice after genetic or pharmacological manipulation. However, because of the potentially confounding effects of repeated testing and natural intra-individual variations in behaviour over time, subjecting mice to a succession of tests is not ideal.
Objectives: The aim of this study was to investigate, in mice, the utility of an integrated apparatus that combines three classical tests of anxiety, the open field, elevated plus maze (EPM) and light/dark box.
Effects of gabapentin and antidepressant drug combinations on convulsions and memory in mice.
Pol J Pharmacol
June 2004
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi-110062, India.
In epileptic patients, neurobehavioral problems such as cognitive impairment, depression, and psychosocial impairments have been described, which may have a pathological and/or iatrogenic basis. For this reason additional treatment is required, beside antiepileptic drug (AED) therapy, to correct the accompanying neurological deficits. However, the rationale behind use of antidepressants along with antiepileptics has been questioned due to proconvulsant effects of the former.
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