Document Detail


Anticonvulsive effect of nonimidazole histamine H3 receptor antagonists.
MedLine Citation:
PMID:  24776492     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
To determine the potential of histamine H3 receptor (H3R) ligands as new antiepileptic drugs (AEDs), aromatic ether, and diether derivatives (1-12) belonging to the nonimidazole class of ligands, with high in-vitro binding affinity at human H3R, were tested for their in-vivo anticonvulsive activity in the maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-kindled seizure models in rats. The anticonvulsive effects of a systemic injection of 1-12 on MES-induced and PTZ-kindled seizures were evaluated against the reference AED phenytoin (PHT) and the structurally related H3R antagonist/inverse agonist pitolisant (PIT). Among the most promising ligands 2, 4, 5, and 11, there was a significant and dose-dependent reduction in the duration of tonic hind limb extension (THLE) in MES-induced seizure subsequent to administration of 4 and 5 [(5, 10, and 15 mg/kg, intraperitoneally (i.p.)]. The protective effects observed for the 1-(3-(3-(4-chlorophenyl)propoxy)propyl)-3-methylpiperidine derivative 11 at 10 mg/kg, i.p. were significantly greater than those of PIT, and were reversed by pretreatment with the central nervous system penetrant H1R antagonist pyrilamine (PYR) (10 mg/kg). Moreover, the protective action of the reference AED PHT, at a dose of 5 mg/kg (without considerable protection in the MES model), was significantly augmented when coadministered with derivative 11 (5 mg/kg, i.p.). Surprisingly, pretreatment with derivative 7 (10 mg/kg, i.p.), an ethylphenoxyhexyl-piperidine derivative without considerable protection in the MES model, potently altered PTZ-kindled seizure, significantly prolonged myoclonic latency time, and clearly shortened the total seizure time when compared with control, PHT, and PIT. These interesting results highlight the potential of H3R ligands as new AEDs or as adjuvants to available AED therapeutics.
Authors:
Bassem Sadek; Kamil Kuder; Dhanasekaran Subramanian; Mohamed Shafiullah; Holger Stark; Dorota Lażewska; Abdu Adem; Katarzyna Kieć-Kononowicz
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Behavioural pharmacology     Volume:  25     ISSN:  1473-5849     ISO Abbreviation:  Behav Pharmacol     Publication Date:  2014 Jun 
Date Detail:
Created Date:  2014-04-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9013016     Medline TA:  Behav Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  245-52     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Developmentally vitamin D-deficient rats show enhanced prepulse inhibition after acute ?9-tetrahydro...
Next Document:  Group B Streptococcal Infection in a Tertiary Hospital in India-1998-2010.