ABSTRACT
A series of benzoazepine derivatives, bearing suitable substituents at the C-3 position, was designed and evaluated by superimposition with the pharmacophore model of the glycine binding site. To fully explore the SAR of this class of compounds and to allow the preparation of new different compounds at the C-3 position, appropriate synthetic routes were set up. The benzoazepines were evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. This further analysis confirmed the preliminary results previously reported and that compound 27 is the most promising compound (Ki=32 nM, ED(50)=0.09 mg/kg, i.v.) in this series. Significant neuroprotective effect was observed after both pre- and post-ischaemia administration in the MCAo model. In particular, after post-ischaemia administration, it was found to be still effective when the administration was delayed up to 6 h after occlusion of the middle cerebral artery.
Subject(s)
Anticonvulsants/chemical synthesis , Azepines/chemical synthesis , Neuroprotective Agents/chemical synthesis , Receptors, Glycine/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Animals , Anticonvulsants/chemistry , Anticonvulsants/pharmacology , Arterial Occlusive Diseases/complications , Azepines/chemistry , Azepines/pharmacology , Binding Sites , Brain Ischemia/drug therapy , Brain Ischemia/etiology , Male , Mice , Middle Cerebral Artery , Models, Molecular , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
BACKGROUND: The internet has been increasingly used as a resource for accessing health-related information. A recent US survey found that approximately half of inflammatory bowel disease (IBD) patients in an IBD clinic use the internet to gather IBD-specific information. AIM: The aim of this study was to evaluate the use of the internet among Italian IBD patients. METHODS: The study was performed in seven Italian IBD referral centers by using a 28-item anonymous questionnaire. RESULTS: In all, 495 questionnaires were returned for analysis, in which 305 of 495 patients (61.6%) indicated that they are able to access the internet. A large proportion used the internet to gather health-related information (180 of 305, 59.1%) and IBD-related information (226 of 305, 74.2%). The use of the internet increased significantly with level of education (P<0.0001) and household income (P<0.0001). In addition, the use of the internet to gather IBD-related information increased significantly with the increase of disease activity and severity. CONCLUSION: Approximately half of the patients in Italian IBD referral centers used the internet to gather IBD-related information. This use positively correlated with disease activity and severity. The great majority of patients indicated that it was very important for IBD referral centers to have their own IBD-dedicated website.