Jordan M Kane

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Selected examples from three series of isomeric (alkylthio)-1,2,4-triazoles were prepared and examined for anticonvulsant activity versus strychnine-, maximal-electroshock-, pentylenetetrazole-, and 3-mercaptopropionic-acid-induced seizures in mice. A number of 5-aryl-3-(alkylthio)-4H-1,2,4-triazoles were selective antagonists of strychnine-induced(More)
1. The present study investigated biochemical, electrophysiological and behavioural properties of the novel cognition enhancer, MDL 26,479 (5-(3-fluorophenyl)-2,4-dimethyl-3H-1,2,4-triazole-3-thione). 2. The 5-aryl-1,2,4-triazole, MDL 26,479, potently (0.22 +/- 0.05 mg kg-1) inhibited [3H]-flumazenil (Ro15-1788) binding in mouse cortex but was ineffective(More)
MDL 26,479, a novel triazole compound with action at the GABAA receptor complex, was examined in 2 models of working memory deficit in the rat. MDL 26,479 attenuated a scopolamine-induced acquisition deficit in a T-maze reinforced alternation task. MDL 26,479 also reversed a performance deficit induced by increased delay between sample and choice trials in(More)
The compound 5-(4-chlorophenyl)-2,4-dihydro-4-ethyl-3H-1,2,4-triazol-3-one (MDL 27,192) was evaluated in a variety of rodent models to assess its anticonvulsant profile and its potential neuroprotective activity. MDL 27,192 demonstrated anticonvulsant activity in a wide range of epilepsy models that are genetically-based (audiogenic seizures in the seizure(More)
A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones was prepared and evaluated for potential antidepressant activity. Members of this series were generally prepared by the alkaline ring closures of the corresponding 1-aroylthiosemicarbazides. Several members of this series were potent antagonists of both RO 4-1284-induced hypothermia and(More)
The fhl1 gene encoding four-and-a-half LIM protein-1 (FHL1) and its spliced isoform, SLIMMER, is mutated in reducing body myopathy, X-linked myopathy with postural muscle atrophy, scapuloperoneal myopathy, and rigid spine syndrome. In this study we have identified a novel function for SLIMMER in delaying skeletal muscle apoptosis via an interaction with the(More)
Disrupted glycinergic inhibition in the brainstem and spinal cord may contribute to some of the alterations in reflex control seen in patients with spastic disorders. MDL 27,531, which acts functionally like a glycine agonist in its capacity to selectively reverse seizures produced by the glycine antagonist strychnine, was evaluated in a model of spinal(More)
1. Strychnine-sensitive glycine receptors are primarily localized in the brainstem and spinal cord where they are the major mediators of postsynaptic inhibition. A compound which acts functionally like a glycine receptor agonist would be potentially useful as a pharmacological tool and as a therapeutic agent for treating disorders of glycinergic(More)
The title compounds were prepared by alkylation of 6-aryl-4,5-dihydro-3(2H)-pyridazinones with esters of alpha-bromoacetic acid. Hydrolysis of these esters afforded the corresponding carboxylic acids which were coupled with various amines yielding 6-oxo-1(4H)-pyridazineacetamides. A number of these derivatives showed weak anticonvulsant and weak analgesic(More)
A series of 5-aryl-2,4-dihydro-3H-1,2,4-triazol-3-ones was evaluated for anticonvulsant activity. In general the members of this series were prepared by the alkaline cyclization of 1-aroyl-4-alkylsemicarbazides. The resulting 2-unsubstituted 3H-1,2,4-triazol-3-ones were then alkylated, yielding 2,4-dialkyl-3H-1,2,4-triazol-3-ones. Approximately one-third of(More)