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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/03/08 14:28:50」(JST)

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Tacrine is a centrally acting anticholinesterase and indirect cholinergic agonist (parasympathomimetic). It was the first centrally-acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease, and was marketed under the trade name Cognex. Tacrine was first synthesised by Adrien Albert at the University of Sydney. It also acts as a histamine N-methyltransferase inhibitor.

Clinical use

Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. Studies found that it may have a small beneficial effect on cognition and other clinical measures, though study data was limited and the clinical relevance of these findings was unclear.^[1]^[2]

The use of tacrine is limited by poor oral bioavailability, the necessity for four-times daily dosing, and considerable adverse drug reactions (including nausea, diarrhea, urinary incontinence and hepatotoxicity) such that few patients could tolerate therapeutic doses.^[3]

Newer cholinesterase inhibitors, such as donepezil, are now preferred over tacrine.

Overdosage/Toxicity

As stated above, overdosage of tacrine may give rise to severe side effects such as nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Tertiary anticholinergics, such as atropine, may be antidotes for overdose.

Major form of metabolism is in the liver via hydroxylation of benzylic carbon by Cytochrome P450 (CYP450). This forms the major metabolite 1-hydroxy-tacrine (velnacrine) which is still active.^{[citation needed]}

References

^ Qizilbash N, Whitehead A, Higgins J, et al. (1998). "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials". Journal of the American Medical Association 280 (20): 1777–82. PMID 9842955.
^ Rang HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology (5th ed. ed.). Edinburgh: Churchill Livingstone. ISBN 9780443071454. .
^ Sweetman S, ed. (2004). Martindale: the complete drug reference (34th ed. ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4.

UpToDate Contents

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English Journal

Thunbergia laurifolia extract ameliorates cognitive and emotional deficits in olfactorectomized mice.

Rojsanga P1, Sithisarn P, Tanaka K, Mizuki D, Matsumoto K.
Pharmaceutical biology.Pharm Biol.2015 Aug;53(8):1141-8. doi: 10.3109/13880209.2014.962059. Epub 2015 Jan 22.
CONTEXT: Thunbergia laurifolia Lindl. (Acanthaceae) is a Thai medicinal plant used for the detoxification of poison which is likely to be beneficial for the treatment of cognitive deficits including Alzheimer's disease.OBJECTIVE: To elucidate the effects of Thunbergia laurifolia leaf extract (TLL) o
PMID 25609149

Involvement of dopaminergic and cholinergic systems in social isolation-induced deficits in social affiliation and conditional fear memory in mice.

Okada R1, Fujiwara H1, Mizuki D1, Araki R2, Yabe T2, Matsumoto K3.
Neuroscience.Neuroscience.2015 Jul 23;299:134-45. doi: 10.1016/j.neuroscience.2015.04.064. Epub 2015 May 2.
Post-weaning social isolation rearing (SI) in rodents elicits various behavioral abnormalities including attention deficit hyperactivity disorder-like behaviors. In order to obtain a better understanding of SI-induced behavioral abnormalities, we herein investigated the effects of SI on social affil
PMID 25943484

Enduring effects of tacrine on cocaine-reinforced behavior: Analysis by conditioned-place preference, temporal separation from drug reward, and reinstatement.

Grasing K1, Yang Y2, He S3.
Pharmacological research : the official journal of the Italian Pharmacological Society.Pharmacol Res.2015 Jul;97:40-7. doi: 10.1016/j.phrs.2015.04.003. Epub 2015 Apr 16.
Previous work by our laboratory has shown that tacrine can produce long-lasting reductions in cocaine-reinforced behavior, when administered to rats as daily intravenous infusions over four days. Tacrine causes dose-related liver toxicity in different species, and its manufacture for human use was r
PMID 25890194

Japanese Journal

Synthesis and Biological Evaluation of New Tacrine Analogues under Microwave Irradiation

ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 65(8), 732-738, 2017
NAID 130005875904

Structure–Antiamnesic Activity Relationship of Iridoid Glycosides from Gardenia Fruits

Chemistry Letters 44(6), 837-839, 2015
NAID 130005074585

Structure-antiamnesic activity relationship of iridoid glycosides from gardenia fruits

Chemistry Letters advpub(0), 2015
NAID 130005062165

Related Pictures

Tacrine; Tetrahydroaminoacridine Alzheimer's Disease on emaze Tacrine Drug Molecule Photograph by Laguna Design COGNEX 30 Pill Images (Orange / Yellow / Capsule-shape) Cognex (tacrine) Drug Side Effects, Interactions, and Medication Information on tacrine: Definition from Answers.com Tacrine Alzheimer's Drug Molecule Photograph by Dr Mark J. Winter

★リンクテーブル★

リンク元	「タクリン」「tetrahydroaminoacridine」
拡張検索	「juxtacrine」「tacrine hydrochloride」

「タクリン」

Tacrine
Systematic (IUPAC) name
	1,2,3,4-tetrahydroacridin-9-amine
Clinical data
Trade names	Cognex
AHFS/Drugs.com	monograph
MedlinePlus	a693039
Pregnancy cat.	C (Au), C (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Oral, rectal
Pharmacokinetic data
Bioavailability	2.4–36% (oral)
Protein binding	55%
Metabolism	Hepatic (CYP1A2)
Half-life	2–4 hours
Excretion	Renal
Identifiers
CAS number	321-64-2
ATC code	N06AA18 N06DA01
PubChem	CID 1935
DrugBank	APRD00690
ChemSpider	1859
UNII	4VX7YNB537
ChEBI	CHEBI:45980
ChEMBL	CHEMBL95
Chemical data
Formula	C13H14N2
Mol. mass	198.264 g/mol
SMILES	eMolecules & PubChem
	InChI InChI=1S/C13H14N2/c14-13-9-5-1-3-7-11(9)15-12-8-4-2-6-10(12)13/h1,3,5,7H,2,4,6,8H2,(H2,14,15) ; Key:YLJREFDVOIBQDA-UHFFFAOYSA-N ;
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