J. Mizoule
Rhône-Poulenc
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Featured researches published by J. Mizoule.
Neuropharmacology | 1985
J. Mizoule; B. Meldrum; Martine Mazadier; M. Croucher; Catherine Ollat; A. Uzan; J.-J. Legrand; Claude Gueremy; G. Le Fur
2-Amino-6-trifluoromethoxy benzothiazole (PK 26124) prevented convulsions induced in rodents by maximal electroshock, inhibitors of the synthesis of gamma-aminobutyric acid (GABA) and ouabain, but was inactive against seizures provoked by GABA antagonists, unlike diazepam, chlordiazepoxide, phenobarbital and valproic acid. 2-Amino-6-trifluoromethoxy benzothiazole prevented seizures induced by sound stimuli in DBA/2 mice (ED50 = 0.66; 2.1 and 4.1 mg/kg, i.p. according to the seizure component), postural seizures in El 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. Indeed, PK 26124 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 PK 26124 (kainate, harmaline), whereas it was 10-20 times more potent than PK 26124 against seizures induced by inhibitors of the synthesis of GABA. Together, these data suggest that PK 26124 possesses antagonistic properties of excitatory dicarboxylic amino acids, which may contribute to its anticonvulsant action.
Neuropharmacology | 1985
J. Mizoule; B. Meldrum; Martine Mazadier; M. Croucher; Catherine Ollat; A. Uzan; J.-J. Legrand; Claude Gueremy; G. Le Fur
Two models have been chosen to study the effect of 2-amino-6-trifluoromethoxy benzothiazole (PK 26124) on excitatory amino acid neurotransmission: the pool of cyclic guanosine monophosphate (cGMP) in the cerebellum and the release of acetylcholine in the striatum and olfactory tubercles. The release of acetylcholine induced by N-methyl-DL-aspartate in the striatum and olfactory tubercles was antagonized by PK 26124 which was less potent on the release of acetylcholine induced electrically. The increase in levels of cGMP in the cerebellum induced by excitatory amino acids such as glutamate and quisqualate was antagonized by PK 26124, but the drug was inactive against N-methyl-DL-aspartate, L-aspartate, kainate and cysteine sulphinate. In vivo it antagonized the increases of cGMP in the cerebellum elicited by all these excitatory compounds. All these results are compatible with a possible antagonism by PK 26124 of the excitatory amino acid neurotransmission and may explain its anticonvulsant properties.
Life Sciences | 1981
G. Le Fur; J. Mizoule; Marie-Claude Burgevin; O. Ferris; Michel Héaulme; A. Gauthier; Claude Gueremy; A. Uzan
Abstract PK 8165 and PK 9084, two quinoline derivatives, displace [ 3 H]-diazepam and its binding sites. These drugs appeared to be more potent in the presence of halides suggesting that they are acting on benzodiazepine receptors associated to a chloride ionophore. Like the benzodiazepines PK 8165 and PK 9084 increase punished responding in the rat conflict procedure but do not produce ataxia or sedation even at doses 5 to 20 times higher than those which are effective in the conflict test. Moreover they do not possess anticonvulsant properties. PK 8165 and PK 9084 do not change cGMP content of the cerebellar cortex and do not antagonize the increase in cGMP induced by the GABA antagonists isoniazid and picrotozin. Thus PK 8165 and PK 9084 “pure anticonflict drugs” might act on GABA-independent benzodiazepine receptors associated to a chloride ionophore.
Life Sciences | 1985
J. Mizoule; A. Gauthier; A. Uzan; Christian Renault; Marie-Christine Dubroeucq; Claude Gueremy; G. Le Fur
The effects of two drugs acting at the peripheral type benzodiazepine binding sites, PK 11195 and RO5-4864, were examined in shock-induced suppression of drinking in rats. These two compounds have opposite effects : RO5-4864 (3.1-1205 mg/kg i.p.) enhanced whereas PK 11195 (25-50 mg/kg i.p.) decreased the punished responding, and PK 11195 (6.25 mg/kg, a dose which did not alter the punished responding) blocked the proconflict action of RO5-4864 (6.25 and 12.5 mg/kg). The effects of RO5-4864 and PK 11195 were not antagonized by RO15-1788, a selective antagonist of the central benzodiazepine site. In addition, PK 11195 (6.25 mg/kg) did not reverse the proconflict effect of two beta-carbolines : beta-CEE and FG 7142. AS picrotoxin did not change the punished responding, these data imply that the effects of RO5-4864 and PK 11195 on the one hand and those of chlordiazepoxide and beta-carbolines on the other hand are differentially mediated and suggest that the peripheral type benzodiazepine binding sites are involved in this conflict model.
Journal of Pharmacology and Experimental Therapeutics | 1979
G Le Fur; Françoise Guilloux; N. Mitrani; J. Mizoule; A. Uzan
Life Sciences | 1984
Jesus Benavides; Françoise Guilloux; D.E. Allam; A. Uzan; J. Mizoule; Christian Renault; Marie-Christine Dubroeucq; Claude Gueremy; G. Le Fur
Archive | 1981
Marie-Christine Dubroeucq; Claude Gueremy; Gérard Le Fur; J. Mizoule
Archive | 1981
Marie-Christine Dubroeucq; Claude Gueremy; Fur Gérard Roger Le; J. Mizoule
Life Sciences | 1982
J. Mizoule; Jean Rataud; G. Le Fur; C. Jozefczak; D. Quarteronet; A. Uzan
Archive | 1981
Marie-Christine Dubroeucq; Claude Gueremy; Fur Gérard Roger Le; J. Mizoule