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

Summary In the present study, l -pGlu-(1-benzyl)- l -His- l -ProNH2 (NP-355), a newer CNS active thyrotropin-releasing hormone (TRH) analog was evaluated for its antiepileptic potential. NP-355 (5, 10 and 20 μmol/kg; i.v.) pretreatment significantly delayed onset and reduced the frequency of convuls...

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Bibliographic Details
Published in:Epilepsy research 2009-12, Vol.87 (2), p.223-233
Main Authors: Rajput, Satyendra Kumar, Singh, Jitendra Narain, Ingole, Shubhada, Jain, Gaurav, Kaur, Navneet, Monga, Vikramdeep, Meena, Chhuttan Lal, Jain, Rahul, Sharma, Shyam Sunder
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Anticonvulsants - administration & dosage
Behavior, Animal - drug effects
Blood Pressure - drug effects
Brain - drug effects
Brain - physiopathology
Cardiovascular system
Cerebral blood flow
Cerebrovascular Circulation - drug effects
Dose-Response Relationship, Drug
DRG neurons
Electrophysiology
Electroshock
Functional observation battery
Ganglia, Spinal - cytology
Ganglia, Spinal - drug effects
Kainic Acid - toxicity
Male
Mice
Motor Activity - drug effects
Neurology
Neurons - drug effects
Pentylenetetrazole - toxicity
Picrotoxin - toxicity
Rats
Rats, Sprague-Dawley
Seizure
Seizures - drug therapy
Seizures - etiology
Sodium current
Statistics, Nonparametric
Thyrotropin-Releasing Hormone - administration & dosage
Thyrotropin-Releasing Hormone - analogs & derivatives
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Summary:Summary In the present study, l -pGlu-(1-benzyl)- l -His- l -ProNH2 (NP-355), a newer CNS active thyrotropin-releasing hormone (TRH) analog was evaluated for its antiepileptic potential. NP-355 (5, 10 and 20 μmol/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 μmol/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 μM) 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.
ISSN:0920-1211
1872-6844
DOI:10.1016/j.eplepsyres.2009.09.007