| 2-(1-Hydroxypentyl)-benzoate increases cerebral blood flow and reduces infarct volume in rats model of transient focal cerebral ischemia. | |
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MedLine Citation:
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PMID: 16527903 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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2-(1-Hydroxypentyl)-benzoate (dl-PHPB), a derivate of 3-n-butylphthalide (dl-NBP), is a novel drug candidate used for treatment of cerebral ischemia. The goal of the present study was to investigate the effects of dl-PHPB on infarct volume, neurological function, and cerebral blood flow (CBF) in transient focal cerebral ischemia. Therefore, an animal model of 2-h middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion was used. Rats received dl-PHPB (1.3, 3.9, or 12.9 mg/kg) intravenously 10 min after the onset of MCAO. Compared with the vehicle control group (37.4%), infarct volume in dl-PHPB-treated groups was reduced significantly and dose-dependently to 25.4, 17.4, and 13.7%, respectively. The changes in neurological deficient were also observed in neurobehavioral test in a dose-dependent manner, and the neuronal score was improved significantly from the vehicle control of 3.2 to 2.7, 2.1, and 1.8, respectively. At the highest dose, the potency of dl-PHPB was similar to those of dl-NBP. CBF was quantified by using laser-Doppler flowmetry. During the ischemia, the regional CBF values of dl-PHPB groups were significantly higher than that of vehicle group. In addition, our study showed that dl-PHPB converted into dl-NBP very quickly in blood in vitro. Approximately 70% of dl-PHPB converted into dl-NBP in 5 min when dl-PHPB was added into plasma at final concentrations of 6, 30, and 60 mug/ml. This result demonstrated that the neuronal protection effects of dl-PHPB were mainly induced by dl-NBP, an active compound converted from its precursor, dl-PHPB. In conclusion, dl-PHPB can reduce infarct volume and improve neurobehavioral deficits in a rat model of transient MCAO. Those effects may partially be due to an increase in CBF by the active metabolite (dl-NBP) of dl-PHPB. Therefore, our results suggest that dl-PHPB may be useful for treatment of ischemia stroke. |
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Authors:
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Yi Zhang; Ling Wang; Jiang Li; Xiao-Liang Wang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-03-09 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 317 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2006 Jun |
Date Detail:
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Created Date: 2006-05-19 Completed Date: 2006-06-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 973-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Benzoates / administration & dosage, pharmacology, therapeutic use* Benzofurans / administration & dosage, pharmacology, therapeutic use* Cerebrovascular Circulation / drug effects* Disease Models, Animal Dose-Response Relationship, Drug Infarction, Middle Cerebral Artery / etiology, prevention & control* Ischemic Attack, Transient* / complications, drug therapy, physiopathology Laser-Doppler Flowmetry Male Neuroprotective Agents / administration & dosage, pharmacology, therapeutic use* Pentanes / administration & dosage, pharmacology, therapeutic use* Prodrugs / administration & dosage, pharmacology, therapeutic use* Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/2-(1-Hydroxypentyl)-benzoate; 0/Benzoates; 0/Benzofurans; 0/Neuroprotective Agents; 0/Pentanes; 0/Prodrugs; 6066-49-5/3-n-butylphthalide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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