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L‐pGlu‐(1‐Benzyl)‐L‐His‐L‐ProNH2: a Newer Thyrotropin‐Releasing Hormone Analog with anticonvulsive and neuroprotective properties
Author(s) -
Rajput Satyendra Kumar,
Singh Jitendra,
Meena Chhuttan,
Jain Rahul,
Pant Aditya,
Sharma Shyam
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.762.9
Subject(s) - neuroprotection , glutamate receptor , kainic acid , viability assay , chemistry , pharmacology , anticonvulsant , kainate receptor , apoptosis , medicine , endocrinology , epilepsy , biochemistry , receptor , psychiatry , ampa receptor
Objective To study the role of L‐pGlu‐(1‐benzyl)‐L‐His‐L‐ProNH 2 (NP‐355) in models of seizures and cellular injury. Methods Seizures were induced in mice by pentylenetetrazole (PTZ; 65mg/kg, ip), picrotoxin (PTX; 3.2 mg/kg, sc) and kainic acid (KA; 35mg/kg, ip). Cerebral blood flow (CBF) was measured with laser Doppler in anaesthetized mice. Sodium current was recorded in cultured neonatal rat dorsal root ganglion neurons (DRG) using whole cell patch clamp technique. Glutamate, H 2 O 2 and oxygen glucose deprivation (OGD)‐induced cell injury was studied in PC‐12 cells using MTT assay. Results NP‐355 pretreatment showed significant protection in PTZ‐, PTX‐ and KA‐ induced seizures, increased the CBF and its exposure produced depression of sodium current in DRG neurons. In vitro , NP‐355 showed protection from glutamate (15mM) ‐ and H 2 O 2 (0.3mM) ‐ induced cellular injury in a time‐ and concentration‐ dependent manner. The maximal protection was observed after 24 hr of incubation and at 10 μM concentration. The cell viability was increased from 36% to 88% and from 54% to 90% after glutamate and H 2 O 2 treatment in presence of NP‐355. Similarly, a significant difference in cell viability was observed in OGD group with (84%) and without (66 %) treatment. NP‐355 didn't show any abnormal effect on CNS. Conclusion NP‐355 is a safe anticonvulsant and neuroprotective agent, also has protective potential against ischemia.