COMPARISON OF THE EFFECTS OF NATURAL AND SYNTHETIC HUPERZINE-A ON RAT-BRAIN CHOLINERGIC FUNCTION IN-VITRO AND IN-VIVO

	COMPARISON OF THE EFFECTS OF NATURAL AND SYNTHETIC HUPERZINE-A ON RAT-BRAIN CHOLINERGIC FUNCTION IN-VITRO AND IN-VIVO
	TANG, XC; KINDEL, GH ; KOZIKOWSKI, AP ; HANIN, I
刊名	JOURNAL OF ETHNOPHARMACOLOGY
	1994-12
卷号	44 期号:3 页码:147-155
关键词	HUPERZINE-A ACETYLCHOLINESTERASE BRAIN CHOLINE ACETYLTRANSFERASE CHOLINERGICS SYNTHETIC ANALOG(S)
ISSN号	0378-8741
文献子类	Article
英文摘要	(-)-Huperzine-A has been shown to be a promising agent for the treatment of dementia of the Alzheimer type. This substance is rare in nature. We have been able to prepare a racemic mixture of(+/-)-huperzine-A in quantity. In the absence of a chiral synthetic procedure for (-)-huperzine-A, this study sought to determine whether the racemic mixture would yield an in vitro and in vivo pharmacological profile of activity similar to that of the natural compound. The synthetic racemic mixture (+/-)-huperzine-A was 3 times less potent than (-)-huperzine-A in vitro (IC50 of 3 x 10(-7) M and 10(-7) M, respectively) because the former consisted of a racemic mixture of the compound in which the (+)-huperzine component was considerably less potent (IC50 = 7 x 10(-6) M). A comparable magnitude of effect was also observed in studies conducted in vivo, in which, over a range of 0.1-2.0 mg/kg administered intraperitoneally (i.p.), both (-)-huperzine-A and (+/-)-huperzine-A exerted significant inhibition of acetylcholinesterase activity, in all brain regions tested (hippocampus, striatum, hypothalamus and frontal cortex). This inhibition of acetylcholinesterase activity was inversely related to levels of acetylcholine measured in the hippocampus and followed the same time course of effect, (-)-Huperzine-A and (+/-)-huperzine-A were shown to be more potent than physostigmine as inhibitors of acetylcholinesterase in vitro (IC50 = 6 X 10(-7) M). Moreover, their inhibitory effect on acetylcholinesterase in vivo was of a longer duration (peak activity of 20 min for physostigmine versus 60 min for the huperzine variants), at the doses tested, Finally, no effect was exerted by either of the huperzine variants on choline acetyltransferase activity in cortex or hippocampus, over a wide range of doses tested (0.1-1.0 mg/kg, i.p.). These findings demonstrate that (+/-)-huperzine-A compares in its activity and biological effects with the natural product, (-)-huperzine-A, both in vitro and in vivo.
资助项目	NIA NIH HHS[AG07591]
WOS关键词	NUCLEUS BASALIS ; SENILE DEMENTIA ; SELECTIVE LOSS ; MEMORY ; CHOLINESTERASE ; ACETYLCHOLINE ; PERFORMANCE ; INHIBITOR ; NEURONS ; DISEASE
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER SCI PUBL IRELAND LTD
WOS记录号	WOS:A1994PY74900004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275083]
专题	中国科学院上海药物研究所
作者单位	1.ACAD SINICA,SHANGHAI INST MAT MED,DEPT PHARMACOL,SHANGHAI 200031,PEOPLES R CHINA 2.MAYO CLIN,DEPT CHEM RES,JACKSONVILLE,FL 32224 3.LOYOLA UNIV,STRITCH SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,MAYWOOD,IL 60153
推荐引用方式 GB/T 7714	TANG, XC,KINDEL, GH,KOZIKOWSKI, AP,et al. COMPARISON OF THE EFFECTS OF NATURAL AND SYNTHETIC HUPERZINE-A ON RAT-BRAIN CHOLINERGIC FUNCTION IN-VITRO AND IN-VIVO[J]. JOURNAL OF ETHNOPHARMACOLOGY,1994,44(3):147-155.
APA	TANG, XC,KINDEL, GH,KOZIKOWSKI, AP,&HANIN, I.(1994).COMPARISON OF THE EFFECTS OF NATURAL AND SYNTHETIC HUPERZINE-A ON RAT-BRAIN CHOLINERGIC FUNCTION IN-VITRO AND IN-VIVO.JOURNAL OF ETHNOPHARMACOLOGY,44(3),147-155.
MLA	TANG, XC,et al."COMPARISON OF THE EFFECTS OF NATURAL AND SYNTHETIC HUPERZINE-A ON RAT-BRAIN CHOLINERGIC FUNCTION IN-VITRO AND IN-VIVO".JOURNAL OF ETHNOPHARMACOLOGY 44.3(1994):147-155.