dizocilpine-maleate and progabide

Digoxin (7.5 micrograms icv) induced 'pop-corn' type of convulsions and 100% mortality. The GABA-ergic agents produced varying degree of protection against digoxin-induced neurotoxicity. Diazepam (4 mg/kg) offered significant protection whereas pentobarbital (5 mg/kg) and baclofen (5 mg/kg) markedly reduced per cent mortality, but ethanol (2 g/kg), progabide (50 mg/kg) and muscimol (0.5 mg/kg) as well as GABA (50 mg/kg) could not offer significant protection in doses used. GABA-ergic agonists; GABA, baclofen, diazepam and pentobarbital when administered along with MK-801 (0.5 mg/kg) a non-competitive NMDA antagonist, a potentiation of anticonvulsant action of MK-801 was observed. MK-801 showed potent anticonvulsant profile in dose range (0.25-1 mg/kg) studied. A synergistic influence of Mg2+ and K+ ions on NMDA receptor antagonism was also observed. A role of GABA-ergic facilitation and NMDA antagonism as a potential anticonvulsant approach in digoxin-induced convulsions in rats has been suggested.

Topics: Animals; Baclofen; Diazepam; Digoxin; Dizocilpine Maleate; Female; gamma-Aminobutyric Acid; Injections, Intraventricular; Male; Muscimol; Pentobarbital; Rats; Rats, Inbred Strains; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; Salts; Seizures

Topics: Amygdala; Animals; Anticonvulsants; Dibenzocycloheptenes; Dizocilpine Maleate; Electroencephalography; Epilepsy; Evoked Potentials; gamma-Aminobutyric Acid; Kindling, Neurologic; Neural Inhibition; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter

Our understanding of how new antiepileptic drugs work mirrors what we know about how currently marketed antiepileptic compounds exert their action--that information is scarce and elusive. The mechanism of action of antiepileptic drugs is nevertheless inextricably linked to epileptogenesis itself, and investigations of several promising new compounds are underway to establish the levels at which these drugs act. Compounds act on synapses and membranes as well as affecting receptors, neurotransmitters, and peptides. The most extensive data are available on drugs that inhibit the action of GABA or its receptors, including new benzodiazepine-like agents and barbituric-acid derivatives. The few drugs that act by inhibiting the effects of excitatory amino acids are reviewed. Finally, the maximal electroshock test is an empirical method to determine the antiepileptic properties of a drug; several agents under development have been effective in this screening technique.

Topics: Acetamides; Acetates; Amines; Aminocaproates; Aminopyridines; Anti-Anxiety Agents; Anticonvulsants; Aspartic Acid; Benzodiazepines; Benzodiazepinones; Clobazam; Cyclohexanecarboxylic Acids; Dibenzocycloheptenes; Dizocilpine Maleate; Epilepsy; Felbamate; Flumazenil; GABA Antagonists; Gabapentin; gamma-Aminobutyric Acid; Glutamates; Glutamic Acid; Imidazoles; Lamotrigine; Phenylcarbamates; Propylene Glycols; Receptors, GABA-A; Triazines; Vigabatrin