| Antiepileptic potential and behavioral profile of L-pGlu-(2-propyl)-L-His-L-ProNH2, a newer thyrotropin-releasing hormone analog. | |
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MedLine Citation:
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PMID: 18952198 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thyrotropin-releasing hormone (TRH) and its analogs have a number of neurobiological functions and therapeutic uses in disorders of the central nervous system. In this study, the newly synthesized TRH analogs were evaluated for central nervous system activity in pentobarbital-induced sleeping in mice. The most potent TRH analog (L-pGlu-(2-propyl)-L-His-L-ProNH(2) coded as NP-647) was evaluated for its antiepileptic potential in various seizure models in mice in comparison with TRH. Intravenous pretreatment with NP-647 (10 and 20 micromol/kg body wt) significantly delayed the onset and reduced the frequency of convulsions in the pentylenetetrazole model, but not in the maximum electroshock seizure model. Also, it was found to be protective against picrotoxin- and kainic acid-induced seizures. However, NP-647 did not significantly affect theophylline-induced seizures. Further study of the effect of NP-647 on locomotor activity and a functional observational battery revealed that it did not significantly exhibit any undesirable effects as compared with vehicle and TRH. NP-647 did not significantly affect cerebral blood flow, whereas the native peptide TRH markedly increased cerebral blood flow. Furthermore, NP-647 exerted antiepileptic activity without significantly altering plasma thyroid-stimulating hormone levels and mean arterial blood pressure. This suggests that NP-647 is more selective for central nervous system activity and devoid of hormonal and cerebrovascular system effects. In contrast, TRH exhibited cardiac and endocrine effects as marked by significant elevation in mean arterial blood pressure and plasma thyroid-stimulating hormone levels. This study demonstrates that NP-647 has potential antiepileptic activity devoid of undesirable effects and, thus, can be exploited for the prevention and treatment of epilepsy. |
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Authors:
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Satyendra Kumar Rajput; Srinivasan Krishnamoorthy; Chandrasekhar Pawar; Navneet Kaur; Vikramdeep Monga; Chhuttan Lal Meena; Rahul Jain; Shyam S Sharma |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-13 |
Journal Detail:
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Title: Epilepsy & behavior : E&B Volume: 14 ISSN: 1525-5069 ISO Abbreviation: Epilepsy Behav Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-12 Completed Date: 2009-04-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100892858 Medline TA: Epilepsy Behav Country: United States |
Other Details:
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Languages: eng Pagination: 48-53 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anticonvulsants / pharmacology*, therapeutic use*, toxicity Behavior, Animal / drug effects Blood Pressure / drug effects Cardiovascular System / drug effects Central Nervous System Stimulants / pharmacology Cerebrovascular Circulation / drug effects Convulsants / antagonists & inhibitors Electroshock Hypnotics and Sedatives / antagonists & inhibitors, pharmacology Kainic Acid / antagonists & inhibitors Male Mice Motor Activity / drug effects Pentylenetetrazole / antagonists & inhibitors Picrotoxin / antagonists & inhibitors Rats Rats, Wistar Seizures / chemically induced, prevention & control Sleep / drug effects Theophylline / antagonists & inhibitors Thyrotropin / blood Thyrotropin-Releasing Hormone / analogs & derivatives*, pharmacology*, therapeutic use, toxicity |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 0/Central Nervous System Stimulants; 0/Convulsants; 0/Hypnotics and Sedatives; 0/pyroglutamyl-(2-propyl)histidyl-prolinamide; 124-87-8/Picrotoxin; 24305-27-9/Thyrotropin-Releasing Hormone; 487-79-6/Kainic Acid; 54-95-5/Pentylenetetrazole; 58-55-9/Theophylline; 9002-71-5/Thyrotropin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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