Reference

2-Amino-6-trifluoromethoxybenzothiazole, a possible antagonist of excitatory amino acid neurotransmission

2-Amino-6-trifluoromethoxybenzothiazole, a possible antagonist of excitatory amino acid neurotransmission. I. Anticonvulsant properties. Mizoule, J.; Meldrum, B.; Mazadier, Martine; Croucher, M.; Ollat, Catherine; Uzan, A.; Legrand, J. J.; Gueremy, C.; Le Fur, G. (Pharmuka Lab., Groupe Rhone Poulenc Sante, Gennevilliers 92231, Fr.). Neuropharmacology, 24(8), 767-73 (English) 1985. CODEN: NEPHBW. ISSN: 0028-3908. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) PK 26124 (I) [1744-22-5] prevented convulsions induced in rodents by maximal electroshock, inhibitors of the synthesis of GABA [56-12-2] and ouabain, but was inactive against seizures provoked by GABA antagonists, unlike diazepam, chlordiazepoxide, phenobarbital, and valproic acid. I prevented seizures induced by sound stimuli in mice (ED50 = 0.66; 2.1 and 4.1 mg/kg, i.p. according to the seizure component), postural seizures in E1 mice (ED50 = 7.5 mg, i.p.), and seizures induced by photic stimulation in the baboon, Papio papio, at 4 and 8 mg/kg (i.v.). This spectrum of anticonvulsant activity closely resembles that reported previously for dicarboxylic amino acid antagonists. I prevented seizures induced by L-glutamate (ED50 = 8.5 mg/kg, i.p.) or by kainate (ED50 = 9.25 mg/kg, i.p.) and tremors induced by harmaline (ED50 = 2.5 mg/kg, i.p.). In these tests diazepam was inactive (L-glutamate) or as potent as I (kainate, harmaline), whereas it was 10-20 times more potent than I against seizures induced by inhibitors of the synthesis of GABA. Together, these data suggest that I possesses antagonistic properties of excitatory dicarboxylic amino acids, which may contribute to its anticonvulsant action.

Riluzole suppresses experimental autoimmune encephalomyelitis: implications for the treatment of multiple sclerosis

Riluzole suppresses experimental autoimmune encephalomyelitis: implications for the treatment of multiple sclerosis. Gilgun-Sherki, Yossi; Panet, Hana; Melamed, Eldad; Offen, Daniel (The Sackler School of Medicine, Rabin Medical Center, Felsenstein Medical Research Center and Department of Neurology, Laboratory of Neurosciences, Tel Aviv University, Petah Tikva 49100, Israel). Brain Research, 989(2), 196-204 (English) 2003 Elsevier Science B.V. CODEN: BRREAP. ISSN: 0006-8993. 1744-22-5 is the cas registry number. This chemical is also mentioned in this article. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Recent studies suggest that glutamate neurotoxicity is involved in the pathogenesis of multiple sclerosis (MS), and that treatment with glutamate receptor (AMPA/kainate) antagonists inhibits exptl. autoimmune encephalomyelitis (EAE), the conventional model of MS. Therefore, we examd. whether riluzole, an inhibitor of glutamate transmission, affects the pathogenesis and clin. features of MS-like disease in myelin oligodendrocyte glycoprotein (MOG)-induced EAE in mice. Here we report that riluzole (10 mg/kg′2/day, i.p.), administered before and even after the appearance of clin. symptoms, dramatically reduced the clin. severity of MOG-induced EAE, while all the MOG-immunized control mice developed significant clin. manifestations. Moreover, the riluzole-treated mice demonstrated only mild focal inflammation, and less demyelination, compared to MOG-treated mice, using histol. methods. Furthermore, riluzole markedly reduced axonal disruption, as assessed by Bielshowesky's silver staining and by antibodies against non-phosphorylated neurofilaments (SMI-32). No difference was detected in the immune system potency, as T-cell proliferative responses to MOG were similar in both groups. In conclusion, our study demonstrates, for the first time, that riluzole can reduce inflammation, demyelination and axonal damage in the CNS and attenuate the clin. severity of MOG-induced EAE. These results suggest that riluzole, a drug used in amyotrophic lateral sclerosis (ALS), might be beneficial for the treatment of MS. .