Tacrine

THA · 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE · Tetrahydroaminoacridine · C01453 · acrine · cs12602 · CS 12602 · AKOS 221-09

https://huagongshe.com/ko/chemical/1935

식별자 및 물리적 특성

CAS No.	206658-92-6
분자식	C13H14N2
평균 분자량	198.26 g/mol
단동위원소 질량	198.11569846 g/mol
SMILES	Nc1c2c(nc3ccccc13)CCCC2
InChIKey	YLJREFDVOIBQDA-UHFFFAOYSA-N
PubChem CID	1935
ChEMBL	CHEMBL1337960
ChEBI	CHEBI:45980
EC No.	206-291-2
DTXSID	DTXSID1037272

화학 및 물리적 성질

XLogP	2.7
극성 표면적	38.9
수소 결합 공여자 수	1
수소 결합 수용자 수	2
회전 가능 결합 수	0
무거운 원자 수	15
형식 전하	0
복잡도	229
의약품	Pharmaceuticals -> Listed in ZINC15
LogP(분배 계수)	2.22.71
용해도	1.36e-01 g/LDMSO(약간 용해됨), 메탄올(약간 용해됨)
녹는점	183.5 °C183.5℃
Physical Description	Solid
Dissociation Constants	9.89.859.95 (at 20 °C)
Collision Cross Section	142.7 Å² [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID1037272]148.62 Å² [M+K]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]
끓는 점	325.59°C (rough estimate)
밀도	0.9827 (rough estimate)
굴절률	1.4400 (estimate)
저장 조건	4°C, away from moisture and light
물리적 상태	고체
pKa(산도 계수)	9+-.0.20(Predicted)
색상	흰색에서 연한 노란색

안전 및 규제

GHS 분류	DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P261, P262, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P316, P318, P319, P321, P330, P332+P317, P337+P317, P361+P364, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard Classes and Categories	Acute Tox. 3 (100%)
Treatment	If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
건강 영향	Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

용도

개요

In the 1950s, tacrine was used experimentally to reverse cholinergic coma in animals. In the 1960s, tacrine was used to reverse the effects of phencyclidine-like drugs. It was also marketed for many years as a respiratory stimulant. In 1993, the US Food and Drug Administration approved tacrine for the treatment of symptoms of mild to moderate Alzheimer’s disease.

용도

The current use of tacrine is limited due to its poor oral bioavailability, the necessity for four daily doses, and serious side effects (including nausea, vomiting, dry mouth, indigestion, diarrhea, loss of appetite, urinary incontinence, collapse, convulsions, and hepatotoxicity). Currently, newer cholinesterase inhibitors (such as donepezil, rivastigmine, and galantamine) are preferred over tacrine.