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Two new hypotheses suggest that the key pathology in migraine has a neuronal origin. A pivotal role is assigned to brain hypoxia (1) and spreading depression (SD) (neuronal depolarization spreading gradually over the cortex) (2). Flunarizine has been tested both against brain hypoxia and SD. Its potent antihypoxic properties in animal models led to its use(More)
Glycogen synthase kinase-3beta (GSK-3beta) is important in neurogenesis. Here we demonstrate that the kinase influenced post-natal maturation and differentiation of neurons in vivo in transgenic mice that overexpress a constitutively active GSK-3beta[S9A]. Magnetic resonance imaging revealed a reduced volume of the entire brain, concordant with a nearly 20%(More)
In animal models of epilepsy the anticonvulsant profile of loreclezole resembles that of barbiturates and benzodiazepines. We examined whether the increase in seizure threshold to pentylenetetrazole infusion produced by 10 mg/kg of loreclezole, pentobarbital or diazepam could be reversed by a spectrum of benzodiazepine partial inverse to full inverse(More)
Transverse hippocampal slices were prepared after 7 days survival from rats subjected to 8 min of global incomplete ischemia by temporary occlusion of both carotid arteries and hypotension. The slices demonstrated a dorsal-ventral gradient in the amount of ischemic neuronal necrosis in the CA1 region. Histologically ischemic cell change decreased from 90%(More)
The preferential alpha 2-noradrenergic agonist clonidine dose-relatedly increased the onset of seizures and mortality times, and decreased severity in rats treated with D,L-allylglycine. These effects were reduced by a dose (2.5 mg/kg) of the preferential alpha 2-antagonist yohimbine, which was itself inactive on the allylglycine seizures. Yohimbine 10(More)
Neurotensin (NT) has been proposed as an endogenous antipsychotic based in part on the similarity in behavioural effects to antipsychotic drugs, for example, attenuation of both amphetamine-induced hyperlocomotion (AH) and amphetamine disrupted pre-pulse inhibition in the rat. However, there is some evidence that repeated administration of NT or an analogue(More)
A pulse-paired stimulation technique was used to examine the in vitro effects of the isomers of etomidate on synaptic transmission between Schaffer collaterals and CA1 pyramidal cells in the guinea pig hippocampus. Etomidate produced a dose-related, stereospecific, reversible increase in paired-pulse inhibition. Replacement of Cl- by isethionate reversed(More)
The effects of nine clinically active antiepileptic drugs and the NMDA antagonist 2-amino-7-phosphonoheptanoic acid (2-APH) were examined in three models in the in vitro hippocampal slice. In the "low Mg2+" model, removal of Mg2+ from the perfusion fluid increased excitatory neurotransmission and led to epileptogenic field potentials. In the "low Ca2+"(More)
In comparison with a series of reference compounds, (2R-trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-Hydroxybutanedioate (R116301) was characterized as a specific, orally, and centrally active neurokinin-1 (NK(1)) receptor antagonist with subnanomolar affinity for the human NK(1)(More)