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.