Ken N Mewett

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Structure/activity relations of agonists and antagonists for the N-methyl-D-aspartate receptor have been investigated by measuring the ability of a large range of substances to inhibit binding of [3H]2-amino-5-phosphonopentanoate to rat brain membranes. A major difference between optimum structures for agonist and antagonist activity lay in the differential(More)
The selective GABA(C) receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA), is eight times more potent against human recombinant p receptors than p2 receptors expressed in Xenopus oocytes. (3-Aminopropyl)methylphosphinic acid (CGP35024), the methylphosphinic acid analogue of GABA, and [(E)-3-aminopropen-1-yl]methylphosphinic(More)
The effects of the enantiomers of (+/-)-CAMP and (+/-)-TAMP [(+/-)-cis- and (+/-)-trans-2-aminomethylcyclopropanecarboxylic acids, respectively], which are cyclopropane analogues of GABA, were tested on GABA(A) and GABA(C) receptors expressed in Xenopus laevis oocytes using two-electrode voltage clamp methods. (+)-CAMP was found to be a potent and full(More)
We report the synthesis of a series of 3-carboxy-, 3-(carboxymethyl)-, 3-(omega-phosphonoalkyl)-1-aminocyclobutane-1-carboxylic acids for evaluation as agonists or antagonists of neurotransmission at excitatory amino acid receptors, particularly N-methyl-D-aspartic acid (NMDA) receptors. The compounds were evaluated as agonists on their ability to(More)
The action of two cyclobutane derivatives of L-glutamic acid on the high affinity uptake of L-glutamic acid was investigated using a preparation of synaptosomes from rat cerebral cortex. cis-1-Aminocyclobutane-1,3-dicarboxylic acid (also known as trans-2,4-methanoglutamic acid) potently inhibited L-glutamic acid uptake (IC50 30 microM), whereas(More)
Structural analogues of ZAPA, Z-3-[(aminoiminomethyl)thio]prop-2-enoic acid, an isothiouronium analogue of GABA, are potent GABAA agonists as seen in the isolated guinea-pig ileum and in the facilitation of [3H]diazepam binding to rat brain membranes. Compounds with guanidino or amidine groups replacing the amino functionality of GABA were also found to be(More)
Three positional isomers (compounds 1, 2, and 3) of 1-uracilylalanine (willardiine) based on a 3-hydroxypyridazine 1-oxide scaffold with an alanine side-chain at positions 4 (1), 5 (2) or 6 (3) were tested for binding to recombinant homomeric AMPA receptor (AMPA-R) subtypes GluR1-4, as well for excitatory activity on the rat cortical wedge preparation. 1(More)
R-(-)-beta-phenyl-GABA has been compared at GABAB receptors using cortical and ileal preparations. R-(-)-beta-phenyl-GABA (EC50 = 25 microM) was a less potent full agonist than R,S-(+/-)-baclofen (EC50 = 2.5 microM), in depressing CA1 population spikes of rat hippocampal slices, and 5 times less potent in attenuating the spontaneous discharges of rat(More)
Purification of a methanol extract from the seed of Idiospermum australiense, guided by bioactivity on a rat brain cortical wedge preparation has afforded two known dimeric alkaloids, the piperidinoindoline (+)-calycanthine [1] and the pyrrolidinoindoline, (-)-chimonanthine [2] along with a new trimeric pyrrolidinoindoline alkaloid, (-)-idiospermuline [3].(More)
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