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: Satyendra Kumar Rajput, Jitendra Narain Singh, Shubhada Ingole, Gaurav Jain, Navneet Kaur, Vikramdeep Monga, Chhuttan Lal Meena, Rahul Jain, Shyam Sunder Sharma
• Journal: Epilepsy research (Epilepsy Res) Vol. 87 Issue 2-3 Pg. 223-33 (Dec 2009) ISSN: 1872-6844 [Electronic] Netherlands
• PMID: 19833480 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• L-pGlu-(1-benzyl)-L-His-L-ProNH2
• Picrotoxin
• Thyrotropin-Releasing Hormone
• Kainic Acid
• Pentylenetetrazole

Topics

• Analysis of Variance
• Animals
• Anticonvulsants (administration & dosage)
• Behavior, Animal (drug effects)
• Blood Pressure (drug effects)
• Brain (drug effects, physiopathology)
• Cerebrovascular Circulation (drug effects)
• Dose-Response Relationship, Drug
• Electrophysiology
• Electroshock
• Ganglia, Spinal (cytology, drug effects)
• Kainic Acid (toxicity)
• Male
• Mice
• Motor Activity (drug effects)
• Neurons (drug effects)
• Pentylenetetrazole (toxicity)
• Picrotoxin (toxicity)
• Rats
• Rats, Sprague-Dawley
• Seizures (drug therapy, etiology)
• Statistics, Nonparametric
• Thyrotropin-Releasing Hormone (administration & dosage, analogs & derivatives)