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Neurosteroids are synthesized in the brain and have been demonstrated to modulate various cerebral functions. Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), a naturally occurring neurosteroid, and ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one), a synthetic derivative, are two neurosteroids acting as positive allosteric modulators(More)
The non-selective alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor antagonists, 2,3-benzodiazepine derivatives CFM-1 (3,5-dihydro-7,8-dimethoxy-1-phenyl-4H-2,3-benzodiazepin-4-one) and CFM-2 (1-(4'-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin -4-one), following intraperitoneal (i.p.) administration, were studied(More)
Imatinib pharmacokinetics (PK) may be affected by a number of factors that are related to the disease being treated and to the response of that disease to imatinib. Patients in the phase I and phase II trials conducted by the EORTC in patients with gastrointestinal stromal tumours (GISTs) and other sarcomas had detailed blood sampling for imatinib PK on day(More)
We have studied the effects of selective and non-selective adenosine receptor agonists and antagonists in audiogenic-seizure-sensitive DBA/2 mice, an animal model of generalized reflex epilepsy. With the exception of the adenosine A3 receptor agonist, N6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (IB-MECA), all the agonists studied prevented the(More)
The two enantiomers of propranolol antagonize generalized tonic-clonic seizures in DBA/2 mice with the (-)-enantiomer being about 1.5 times more potent than the (+)-enantiomer. Metoprolol was less active and atenolol was unable to affect audiogenic seizures. In combination with conventional antiepileptic drugs, both propranolol enantiomers tested in doses(More)
Microinjection of N-methyl-D-aspartate (NMDA; 1 and 2.5 nmol) or kainate (KA; 50 pmol) into the deep prepiriform cortex elicited behavioral signs of seizure activity. No epileptiform activity was observed after deep prepiriform cortex microinjection of either L-arginine (L-Arg, 5 and 10 nmol) or its D-enantiomer, D-arginine (D-Arg, 2.5-10 nmol). However,(More)
PURPOSE Epilepsy is a heterogeneous syndrome characterized by recurrent, spontaneous seizures; continuous medication is, therefore, necessary, even after the seizures have long been suppressed with antiepileptic drug (AED) treatments. The most disturbing issue is the inability of AEDs to provide a persistent cure, because these compounds generally suppress(More)
Inducible nitric oxide synthase knock-out (iNOS(-/-)) mice are valid models of investigation for the role of iNOS in patho-physiological conditions. There are no available data concerning neuroactive amino acid levels of iNOS(-/-) mice and their behaviour in response to pentylenetetrazole (PTZ). We found no significant differences in the convulsive dose 50(More)
In the present study, the susceptibility of knockout interleukin-6 (IL-6(-/-)) mice to various convulsant stimuli has been evaluated and compared with other three related mice strains. Animals were treated with chemical convulsants impairing the gamma-aminobutyric acid neurotransmission [pentylenetetrazole (PTZ), picrotoxin, bicuculline,(More)
Interleukin-6-deficient (IL-6(-/-)) mice and their normal littermate (WT) were studied to evaluate their susceptibility to seizures induced by electroshock and audiogenic stimuli at different ages. No significant changes in maximal electroshock susceptibility were evidenced between the two strains, while audiogenic seizures (AGS) can be induced only in(More)