ハロペリドール

ハロペリドール · γ-[4-(p-クロロフェニル)-4-ヒドロキシピペリジノ]-4'-フルオロブチロフェノン · 4-[4-(4-クロロフェニル)-4-ヒドロキシピペリジン-1-イル]-1-(4-フルオロフェニル)ブタン-1-オール · 4-(4-クロロフェニル)-1-[4-(4-フルオロフェニル)-4-ヒドロキシブチル]ピペリジン-4-オール · γ-[4-ヒドロキシ-4-(4-クロロフェニル)ピペリジノ]-4'-フルオロブチロフェノン · 4-[4-(4-クロロフェニル)-4-ヒドロキシ-1-ピペリジニル]-1-(4-フルオロフェニル)-1-ブタノール · ジヒドロハロペリドール · 還元ハロペリドール

https://huagongshe.com/ja/chemical/3559

識別子と物理属性

CAS No.	52-86-8
分子式	C21H23ClFNO2
平均分子量	375.9 g/mol
単同位体質量	375.1401348 g/mol
SMILES	O=C(CCCN1CCC(O)(c2ccc(Cl)cc2)CC1)c1ccc(F)cc1
InChIKey	LNEPOXFFQSENCJ-UHFFFAOYSA-N
PubChem CID	3559
ChEMBL	CHEMBL54
ChEBI	CHEBI:5613
EC No.	200-155-6
DTXSID	DTXSID4034150
現地名	ハロペリドール

化学・物理的性質

XLogP	3.2
極性表面積	40.5
水素結合供与体数	1
水素結合受容体数	4
回転可能結合数	6
重原子数	26
形式電荷	0
複雑度	451
医薬品	DEA NFLIS-Drug Category -> Depressants and TranquilizersPharmaceuticals -> AntipsychoticsPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Nervous system -> Antipsychotics
LogP（分配係数）	log Kow = 4.303.23
Color/Form	CrystalsWHITE TO FAINTLY YELLOWISH, AMORPHOUS OR MICRO-CRYSTALLINE POWDER
溶解度	Crystalsmp 226-227.5 °Csol in water at 300X10+1 mg/L /Hydrochloride/In water, 1.4X10+1 mg/L @ 25 °C16.7 mg/ml in alcohol at 25 °CFreely sol in chloroform, methanol, acetone, benzene, dil acids4.46e-03 g/L45% (w/v) 2-ヒドロキシプロピル-β-シクロデキストリン水溶液: 0.39 mg/mL2.058mg/L(22.5℃)
Human Drugs	Breast FeedingLactationMilk, HumanAntipsychotic AgentsButyrophenonesFDA approved drugs -> Active ingredientPharmaceuticalsMedicines for other common symptoms in palliative care
融点	151.5 °C152 °C
蒸気圧	4.8X10-11 mm Hg @ 25 °C /Estimated/
ヘンリー定数	Henry's Law constant = 2.3X10-14 atm-cu m/mol @ 25 °C /Estimated/
Physical Description	Solid
Ionization Efficiency	Positive4.265924542.7Thermo LTQElectrospray ionizationformic acid (5.3nM)
Dissociation Constants	8.658.58.66pKa= 8.66
Collision Cross Section	200.2 Å² [M+Na]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID4034150]193.7 Å² [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]185.12 Å² [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]191.7 Å² [M+H]+ [CCS Type: TW193.9 Å² [M+H]+ [CCS Type: TW]194.1 Å² [M+H]+ [CCS Type: DTMethod: single field calibrated]
沸点	529.0±50.0 °C(Predicted)
密度	1.1820 (estimate)
引火点	9℃
貯蔵条件	2-8°C
外観・状態	粉
pKa（酸解離定数）	8.3(at 25℃)
色	白い
Merck	14,4598
ヘンリー定数	4.3×108 mol/(m3Pa) at 25℃, HSDB (2015)
BCS Class	4/3
主な用途	医薬品（低分子化合物）
InChI	1S/C21H23ClFNO2/c22-18-7-5-17(6-8-18)21(26)11-14-24(15-12-21)13-1-2-20(25)16-3-9-19(23)10-4-16/h3-10,26H,1-2,11-15H2
InChIKey	LNEPOXFFQSENCJ-UHFFFAOYSA-N
SMILES	OC1(CCN(CCCC(=O)c2ccc(F)cc2)CC1)c3ccc(Cl)cc3
CAS データベース	52-86-8(CAS DataBase Reference)
NISTの化学物質情報	Haloperidol(52-86-8)
EPAの化学物質情報	Haloperidol (52-86-8)

化学的特性

White Crystalline Powder

安全性と法規制

GHS 分類	This chemical does not meet GHS hazard criteria for 2.4% (2 of 85) of reports.DangerH301 (97.6%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P261, P264, P264+P265, P270, P271, P272, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 85 reports by companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
規制情報	Hazard Traits - Developmental ToxicityReproductive ToxicityHaloperidol: Does not have an individual approval but may be used under an appropriate group standard
その他の安全情報	IMAP assessments - 1-Butanone, 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-: Environment tier I assessment
FDA 要件	The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl haloperidol, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
Special Reports	Jann MW, Richards ALUS Pharm 10 (Jan): PH1-5, H9, H12-H13 (1985). A review of the pharmacology, pharmacokinetics, dosage and side effects of haloperidol, loxapine, thiothixene and fluphenazine is presented along with the role of clinical pharmacists in the appropriate use and selection of antipsychotics in emergency medical situations and psychiatric crises.Markowitz JC, Brown RPGen Hosp Psychiatry 9 (2): 135-41 (1987). The authors review the literature associating neuroleptic and antidepressant medications with seizures, discussing the relative "seizurogenicity" of different medications, risk factors for seizures, and drugs of choice for high-risk patients. Case histories are presented.
Hazard Classes and Categories	Acute Tox. 3 (97.6%)Acute toxicity (Oral) - Category 4
処分方法	SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality

用途

解説

ハロペリドール,ブチロフェノン誘導体の抗精神病薬の一つである (→向精神薬 ) 。作用機序として，抗ドーパミン，抗ヒスタミン作用のほか，弱いが抗αアドレナリン，抗セロトニン作用が考えられている。臨床では，精神病治療のほかに強化麻酔，止痒，制吐などに用いられる。抗精神病薬の原型であるクロルプロマジンと作用も副作用も類似しており，強弱の差があるだけである。ハロペリドールのほうが，副作用としての鎮静作用は弱く，パーキンソン症状は強く，起立性低血圧は軽度である。

用途

神経化学研究用。

用途

抗精神病薬,精神安定剤

用途

ブチロフェノン系化合物です。ドパミンD2 受容体遮断作用を示します。

用途

ブチロフェノン系化合物です。ドーパミンD2 受容体遮断作用を示します。

説明

Haloperidol is a butyrophenone with a long duration of action. It has lile α- adrenoceptor blocking activity and minimal effect on the cardiovascular system. It is an effective antiemetic but has a high incidence of extrapyramidal adverse effects. Haloperidol may be used in the short-term management of the acutely agitated patient (when sinister causes of confusion such as hypoxaemia and sepsis have been excluded) and in the management of delirium in ICU. The duration of action of haloperidol is approximately 24–48h.

来歴

Haloperidol (brand name Haldol) was first approved by the FDA on April 12, 1967, for the treatment of schizophrenia. It is a typical antipsychotic drug. However, due to its severe neurotoxicity and significant harm to the human body, it has gradually been phased out of the market. Haldol is also approved by the FDA for Tourette syndrome and hyperactivity or severe behavioral problems in children who are unresponsive to treatment or other medications. However, this drug can only be obtained through a doctor's prescription.

使用

Haloperidol is one of the most actively used modern neuroleptics. Its high antipsychotic activity is combined with a moderate sedative effect. It effectively stops various types of psychomotor excitement. It is used for schizophrenic psychoses, manic, paranoid, and delirious conditions, depression, psychomotor excitement of various origins, and for delirium and hallucinations of different origin.

一般的な説明

Haloperidol, 4-[4-(p-chlorophenyl)-4-hydroxypiperidino]-4-fluorobutyrophenone (Haldol), is anodorless white to yellow crystalline powder. Haloperidol iswell and rapidly absorbed and has a high bioavailability. It ismore than 90% bound to plasma proteins. Haloperidol is excretedslowly in the urine and feces. About 30% of a dose isexcreted in urine and about 20% of a dose in feces via biliaryelimination,and only 1% of a dose is excreted as unchangeddrug in the urine.Haloperidol is a minor substrate of CYP1A2 and a major substrate of CYP2D6 and CYP3A4.CYP2D6 inhibitors may increase the levels/effects ofhaloperidol.Haloperidol may increase the levels/effects ofCYP2D6 substrates and it may decrease the bioactivationof CYP2D6 prodrugs substrates. Haloperidol also is a moderateinhibitor of CYP2D6 and CYP3A4. CYP3A4 inducersmay decrease the levels/effects of haloperidol, whereasCYP3A4 inhibitors may increase the levels/effects ofhaloperidol. Centrally acting acetylcholinesterase inhibitorsmay increase the risk of antipsychotic-related EPS. The precisemechanism of antipsychotic action is unclear but isconsidered to be associated with the potent DA D2receptor–blocking activity in the mesolimbic system and theresulting adaptive changes in the brain. Haloperidol is usedprimarily for the long-term treatment of psychosis and is especiallyuseful in patients who are noncompliant with theirdrug treatment.