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.
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.
Rajput
Satyendra Kumar
SK
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India.
Singh
Jitendra Narain
JN
Ingole
Shubhada
S
Jain
Gaurav
G
Kaur
Navneet
N
Monga
Vikramdeep
V
Meena
Chhuttan Lal
CL
Jain
Rahul
R
Sharma
Shyam Sunder
SS
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*
D000927:Anticonvulsants; D007608:Kainic Acid; D010433:Pentylenetetrazole; D010852:Picrotoxin; D013973:Thyrotropin-Releasing Hormone; C547125:L-pGlu-(1-benzyl)-L-His-L-ProNH2