The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform

Pierre Carpentier - One of the best experts on this subject based on the ideXlab platform.

  • review of the value of Gacyclidine gk 11 as adjuvant medication to conventional treatments of organophosphate poisoning primate experiments mimicking various scenarios of military or terrorist attack by soman
    Neurotoxicology, 1999
    Co-Authors: Guy Lallement, Dominique Baubichon, Didier Clarencon, Monique Galonnier, Michel Peoch, Pierre Carpentier
    Abstract:

    Today, organophosphorus nerve agents are still considered as potential threats in both military or terrorism situations. These agents act as potent irreversible inhibitors of acetylcholinesterase in both central and peripheral nervous systems. Conventional treatment of organophosphate poisoning includes the combined administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). However, numerous studies have demonstrated that the excitatory amino acid glutamate also plays a prominent role in the maintenance of organophosphate-induced seizures and in the subsequent neuropathology especially through an overactivation of the N-methyl-D-aspartate (NMDA) receptor subtype. Contrary to other non-competitive NMDA antagonists successfully tested in rodents exposed to organophosphate, Gacyclidine is a novel antiNMDA compound which is in the process of approval for human use in France for neurotraumatology. This review summarizes the therapeutic value of Gacyclidine as a complement to the available emergency treatment against severe organophosphate poisoning. Previous data obtained from experiments on primates in several scenarios mimicking military or terrorist attacks, using soman as the nerve agent, were used. Primates pretreated with pyridostigmine and receiving conventional emergency therapy at the first signs of poisoning survive. However, only Gacyclidine is able to ensure complete management of nerve agent poisoning for rapid normalization of EEG activity, clinical recovery and neuroprotection. Gacyclidine also ensures optimal management of severe nerve agent poisoning in animals neither pretreated nor receiving emergency therapy likewise during an unexpected exposure. However, this beneficial effect is obtained provided that medical intervention is conducted rapidly after intoxication. Globally, the current lack of any other NMDA receptor antagonist suitable for human use reinforces the therapeutic value of Gacyclidine as a central nervous system protective agent for the treatment of OP poisoning.

Jeffrey S. Smith - One of the best experts on this subject based on the ideXlab platform.

  • Effects of the Novel NMDA Receptor Antagonist Gacyclidine on Recovery from Medial Frontal Cortex Contusion Injury in Rats
    2013
    Co-Authors: Jeffrey S. Smith, Steven A. Levinsohn, Zoltan Fulop L. L, Richard Darrell S. L, Donald Stein G. ’t
    Abstract:

    Gacyclidine, a novel, noncompetitive NMDA receptor antagonist, was injected (i.v.) into rats at three different doses to determine if the drug could promote behavioral recovery and reduce the behavioral and anatomical impairments that occur after bilateral contusions of the medial frontal cortex (MFC). In the Morris water maze, contused rats treated with Gacyclidine at a dosage of 0.1 mg/kg performed better than their vehicle-treated conspecifics. Rats given Gacyclidine at either 0.3 or 0.03 mg/kg performed better than brain-injured controls, but not as well as those treated with 0.1 mg/kg. Counts of surviving neurons in the nucleus basalis magnoceilularis (NBM) and the medial dorsal nucleus (MDN) of the thalamus were used to determine whether Gacyclidine treatment attenuated secondary cell death. In both the NBM and the MDN, the counts revealed fewer surviving neurons in untreated contused rats than in Gacyclidine-treated rats. Increases in the size and number of microglia and astrocytes were observed in the striatum of Gacyclidinetreated contused brains. Although most consequences of MFC contusions were attenuated, we still observed increases in ventricle dilation and thinning of the cortex. tCorresponding author

  • Effects of the Novel NMDA Receptor Antagonist Gacyclidine on Recovery From Medial Frontal Cortex Contusion Injury in Rats
    Hindawi Limited, 2000
    Co-Authors: Jeffrey S. Smith, Zoltan L. Fulop, Steven A. Levinsohn, Richard S. Darrell, Donald G. Stein
    Abstract:

    Gacyclidine, a novel, noncompetitive NMDA receptor antagonist, was injected (i.v.) into rats at three different doses to determine if the drug could promote behavioral recovery and reduce the behavioral and anatomical impairments that occur after bilateral contusions of the medial frontal cortex (MFC). In the Morris water maze,contused rats treated with gacyciidine at a dosage of 0.1 mg/kg performed better than their vehicle-treated conspecifics. Rats given Gacyclidine at either 0,3 or 0.03 mg/kg performed better than brain-injured controls, but not as well as those treated with 0.1 mg/kg. Counts of surviving neurons in the nucleus basalis magnoceilularis (NBM) and the medial dorsal nucleus (MDN) of the thalamus were used to determine whether Gacyclidine treatment attenuated secondary cell death. In both the NBM and the MDN, the counts revealed fewer surviving neurons in untreated contused rats than in Gacyclidine-treated rats. Increases in the size and number of microglia and astrocytes were observed in the striatum of Gacyclidinetreated contused brains. Although most consequences of MFC contusions were attenuated, we still observed increases in ventricle dilation and thinning of the cortex. In fact, the ventricles of rats treated with 0.1 mg/kg of Gacyclidine were larger than those of their vehicle treated counterparts, although we observed no behavioral impairment

Guy Lallement - One of the best experts on this subject based on the ideXlab platform.

  • review of the value of Gacyclidine gk 11 as adjuvant medication to conventional treatments of organophosphate poisoning primate experiments mimicking various scenarios of military or terrorist attack by soman
    Neurotoxicology, 1999
    Co-Authors: Guy Lallement, Dominique Baubichon, Didier Clarencon, Monique Galonnier, Michel Peoch, Pierre Carpentier
    Abstract:

    Today, organophosphorus nerve agents are still considered as potential threats in both military or terrorism situations. These agents act as potent irreversible inhibitors of acetylcholinesterase in both central and peripheral nervous systems. Conventional treatment of organophosphate poisoning includes the combined administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). However, numerous studies have demonstrated that the excitatory amino acid glutamate also plays a prominent role in the maintenance of organophosphate-induced seizures and in the subsequent neuropathology especially through an overactivation of the N-methyl-D-aspartate (NMDA) receptor subtype. Contrary to other non-competitive NMDA antagonists successfully tested in rodents exposed to organophosphate, Gacyclidine is a novel antiNMDA compound which is in the process of approval for human use in France for neurotraumatology. This review summarizes the therapeutic value of Gacyclidine as a complement to the available emergency treatment against severe organophosphate poisoning. Previous data obtained from experiments on primates in several scenarios mimicking military or terrorist attacks, using soman as the nerve agent, were used. Primates pretreated with pyridostigmine and receiving conventional emergency therapy at the first signs of poisoning survive. However, only Gacyclidine is able to ensure complete management of nerve agent poisoning for rapid normalization of EEG activity, clinical recovery and neuroprotection. Gacyclidine also ensures optimal management of severe nerve agent poisoning in animals neither pretreated nor receiving emergency therapy likewise during an unexpected exposure. However, this beneficial effect is obtained provided that medical intervention is conducted rapidly after intoxication. Globally, the current lack of any other NMDA receptor antagonist suitable for human use reinforces the therapeutic value of Gacyclidine as a central nervous system protective agent for the treatment of OP poisoning.

Donald Stein G. ’t - One of the best experts on this subject based on the ideXlab platform.

  • Effects of the Novel NMDA Receptor Antagonist Gacyclidine on Recovery from Medial Frontal Cortex Contusion Injury in Rats
    2013
    Co-Authors: Jeffrey S. Smith, Steven A. Levinsohn, Zoltan Fulop L. L, Richard Darrell S. L, Donald Stein G. ’t
    Abstract:

    Gacyclidine, a novel, noncompetitive NMDA receptor antagonist, was injected (i.v.) into rats at three different doses to determine if the drug could promote behavioral recovery and reduce the behavioral and anatomical impairments that occur after bilateral contusions of the medial frontal cortex (MFC). In the Morris water maze, contused rats treated with Gacyclidine at a dosage of 0.1 mg/kg performed better than their vehicle-treated conspecifics. Rats given Gacyclidine at either 0.3 or 0.03 mg/kg performed better than brain-injured controls, but not as well as those treated with 0.1 mg/kg. Counts of surviving neurons in the nucleus basalis magnoceilularis (NBM) and the medial dorsal nucleus (MDN) of the thalamus were used to determine whether Gacyclidine treatment attenuated secondary cell death. In both the NBM and the MDN, the counts revealed fewer surviving neurons in untreated contused rats than in Gacyclidine-treated rats. Increases in the size and number of microglia and astrocytes were observed in the striatum of Gacyclidinetreated contused brains. Although most consequences of MFC contusions were attenuated, we still observed increases in ventricle dilation and thinning of the cortex. tCorresponding author

Donald G. Stein - One of the best experts on this subject based on the ideXlab platform.

  • Effects of the Novel NMDA Receptor Antagonist Gacyclidine on Recovery From Medial Frontal Cortex Contusion Injury in Rats
    Hindawi Limited, 2000
    Co-Authors: Jeffrey S. Smith, Zoltan L. Fulop, Steven A. Levinsohn, Richard S. Darrell, Donald G. Stein
    Abstract:

    Gacyclidine, a novel, noncompetitive NMDA receptor antagonist, was injected (i.v.) into rats at three different doses to determine if the drug could promote behavioral recovery and reduce the behavioral and anatomical impairments that occur after bilateral contusions of the medial frontal cortex (MFC). In the Morris water maze,contused rats treated with gacyciidine at a dosage of 0.1 mg/kg performed better than their vehicle-treated conspecifics. Rats given Gacyclidine at either 0,3 or 0.03 mg/kg performed better than brain-injured controls, but not as well as those treated with 0.1 mg/kg. Counts of surviving neurons in the nucleus basalis magnoceilularis (NBM) and the medial dorsal nucleus (MDN) of the thalamus were used to determine whether Gacyclidine treatment attenuated secondary cell death. In both the NBM and the MDN, the counts revealed fewer surviving neurons in untreated contused rats than in Gacyclidine-treated rats. Increases in the size and number of microglia and astrocytes were observed in the striatum of Gacyclidinetreated contused brains. Although most consequences of MFC contusions were attenuated, we still observed increases in ventricle dilation and thinning of the cortex. In fact, the ventricles of rats treated with 0.1 mg/kg of Gacyclidine were larger than those of their vehicle treated counterparts, although we observed no behavioral impairment