title: Neuropharmacological profile of L-pGlu-(1-benzyl)-L-His-L-ProNH2, a newer thyrotropin-releasing hormone analog: effects on seizure models, sodium current, cerebral blood flow and behavioral parameters.
abstract: In the present study, L-pGlu-(1-benzyl)-L-His-L-ProNH(2) (NP-355), a newer CNS active thyrotropin-releasing hormone (TRH) analog was evaluated for its antiepileptic potential. NP-355 (5, 10 and 20 micromol/kg; i.v.) pretreatment significantly delayed onset and reduced the frequency of convulsions in pentylenetetrazole-induced seizures. NP-355 was also found to be protective against picrotoxin- and kainic acid-induced seizures. Maximum electroshock-induced seizures were not protected even at 20 micromol/kg in mice. Effects of NP-355 on functional observation battery did not exhibit any undesirable effects. Moreover, the antiepileptic activity produced by NP-355 was observed without significantly altering mean arterial blood pressure. NP-355 significantly increases the CBF to 17+/-3% as compared to saline (6+/-2%). NP-355 (100, 300 and 1000 microM) produces a concentration-dependent depression (16%, 63% and 77%, respectively) of the peak sodium current. NP-355 did not alter neurobehavioral parameters. This study demonstrates that NP-355 has potential antiepileptic activity and devoid of undesirable effects.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India.
authors.forename: Satyendra Kumar
authors.initials: SK
authors.lastname: Rajput
authors.forename: Jitendra Narain
authors.initials: JN
authors.lastname: Singh
authors.forename: Shubhada
authors.initials: S
authors.lastname: Ingole
authors.forename: Gaurav
authors.initials: G
authors.lastname: Jain
authors.forename: Navneet
authors.initials: N
authors.lastname: Kaur
authors.forename: Vikramdeep
authors.initials: V
authors.lastname: Monga
authors.forename: Chhuttan Lal
authors.initials: CL
authors.lastname: Meena
authors.forename: Rahul
authors.initials: R
authors.lastname: Jain
authors.forename: Shyam Sunder
authors.initials: SS
authors.lastname: Sharma
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004597:Electroshock; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010433:Pentylenetetrazole / Q000633:toxicity; D010852:Picrotoxin / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D018709:Statistics, Nonparametric; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D000927:Anticonvulsants; D007608:Kainic Acid; D010433:Pentylenetetrazole; D010852:Picrotoxin; D013973:Thyrotropin-Releasing Hormone; C547125:L-pGlu-(1-benzyl)-L-His-L-ProNH2