苯哌利多

苯哌利多
临床资料
商品名（英语：Drug nomenclature）	Anquil, Frenactil
AHFS/Drugs.com	国际药品名称
给药途径	口服
ATC码	N05AD07 (WHO) ;
法律规范状态
法律规范	澳：S4 (Prescription only); 美：处方药（℞-only）;
药物动力学数据
生物半衰期	8小时
识别信息
	IUPAC命名法 11-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl1,3-dihydro-2H-benzimidazol-2-one; 1-(1-(4-(4-氟苯基)-4-氧代丁基)哌啶-4-基)-1,3-二氢-2H-苯并咪唑-2-酮; ;
CAS号	2062-84-2
PubChem CID	16363;
DrugBank	DB12867 ;
ChemSpider	15521 ;
UNII	97O6X78C53;
KEGG	D02627;
ChEBI	CHEBI:93403;
ChEMBL	ChEMBL297302 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID7045364 ;
ECHA InfoCard	100.016.521
化学信息
化学式	C22H24FN3O2
摩尔质量	381.45 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES Fc1ccc(cc1)C(=O)CCCN4CCC(N3c2ccccc2NC3=O)CC4;
	InChI InChI=1S/C22H24FN3O2/c23-17-9-7-16(8-10-17)21(27)6-3-13-25-14-11-18(12-15-25)26-20-5-2-1-4-19(20)24-22(26)28/h1-2,4-5,7-10,18H,3,6,11-15H2,(H,24,28) ; Key:FEBOTPHFXYHVPL-UHFFFAOYSA-N ;

苯哌利多（INN：benperidol）,商品名Anquil等^[1]。为第一代抗精神病药物，主要用于治疗性欲亢进^[2]和精神分裂症^[3]。苯哌利多为一种强效丁酰苯衍生物，是欧洲市场上的强效神经安定药，氯丙嗪当量达75-100%（约每剂量氟哌啶醇效力的150-200%）^[4]。有时被作为色普龙等抗雄激素药的替代方案，作为假释条件开给性罪犯者^[5]。

苯哌利多于1961年由比利时杨森制药公司发现，并于1966年投入市场。主要销往德国，在比利时、希腊、意大利、荷兰和英国也可获得^[6]。

药理学

药效动力学

苯哌利多是强效多巴胺受体激动剂（D₂，K_i=0.027 nM; D₄，K_i=0.066 nM）,对血清素受体激动性很弱（5-HT_2A, K_i= 3.75 nM）^[7]。在高剂量下，具有抗组胺和α-肾上腺素能特性。其具有最小的抗胆碱性能^[8]。

苯哌利多受体抑制常数^[9]
作用位点	抑制常数K_i (nM)	作用	参考文献
5-羟色胺受体2A（5-HT_2A）	3.75	拮抗作用	^[7]
多巴胺受体D₁	4,100	拮抗作用	^[7]
多巴胺受体D₂	0.027	拮抗作用	^[7]
多巴胺受体D₄	0.06	拮抗作用	^[7]

药代动力学

苯哌利多吸收良好，并经过广泛的首过代谢。1%的药物经肾脏以从尿液排出。生物半衰期为8小时^[8]。

合成

苯哌利多由4-（2-酮酸-1-苯并咪唑）哌啶(1)与4-氯对氟苯丁酮(2)经烷基化反应得到^[10]^[11]。

图中 MIBK=甲基异丁基酮，KI=碘化钾、TM=目标分子，即苯哌利多

参考文献

^ Council A, Kuenssberg V. Benperidol - a drug for sexual offenders?. Drug and Therapeutics Bulletin (BMJ Publishing Group Ltd). 1974-02-01, 12 (3): 12. PMID 4457302. S2CID 44581451. doi:10.1136/dtb.12.3.12.
^ British National Formulary (49th), British Medical Association 2005 p 183
^ Bobon J, Collard J, Lecoq R. [Benperidol and promazine: a "double blind" comparative study in mental geriatrics]. Acta Neurologica et Psychiatrica Belgica. October 1963, 63: 839–43. PMID 14092279 （法语）.
^ Möller HJ, Müller WE, Bandelow. Neuroleptika: pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen; mit 136 Tabellen.. Wiss. Verlag-Ges. 2001. ISBN 3-8047-1773-X （德语）.
^ Murray MA, Bancroft JH, Anderson DC, Tennent TG, Carr PJ. Endocrine changes in male sexual deviants after treatment with anti-androgens, oestrogens or tranquillizers. The Journal of Endocrinology. November 1975, 67 (2): 179–88. PMID 1107462. doi:10.1677/joe.0.0670179.
^ NCATS Inxight Drugs — BENPERIDOL. [13 March 2022].
^ ^7.0 ^7.1 ^7.2 ^7.3 ^7.4 Li P, Snyder GL, Vanover KE. Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future. Current Topics in Medicinal Chemistry. December 2016, 16 (29): 3385–3403. PMC 5112764  . PMID 27291902. doi:10.2174/1568026616666160608084834.
^ ^8.0 ^8.1 Leucht S, Hartung B. Benperidol for schizophrenia. The Cochrane Database of Systematic Reviews. April 2005, 2005 (2): CD003083. PMC 7017029  . PMID 15846648. doi:10.1002/14651858.CD003083.pub2.
^ Roth BL, Driscol J. PDSP K_i Database. Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. [11 March 2022].
^ Thieme
^ BE 626307 (1963 to Janssen), C.A. 60, 10690c (1964), corresp. to GB 989755,“1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds”,发表于1965-04-22,指定于Janssen Pharmaceuticals#History

[1] Council A, Kuenssberg V. Benperidol - a drug for sexual offenders?. Drug and Therapeutics Bulletin (BMJ Publishing Group Ltd). 1974-02-01, 12 (3): 12. PMID 4457302. S2CID 44581451. doi:10.1136/dtb.12.3.12.

[2] British National Formulary (49th), British Medical Association 2005 p 183

[pmid14092279-3] Bobon J, Collard J, Lecoq R. [Benperidol and promazine: a "double blind" comparative study in mental geriatrics]. Acta Neurologica et Psychiatrica Belgica. October 1963, 63: 839–43. PMID 14092279 （法语）.

[4] Möller HJ, Müller WE, Bandelow. Neuroleptika: pharmakologische Grundlagen, klinisches Wissen und therapeutisches Vorgehen; mit 136 Tabellen.. Wiss. Verlag-Ges. 2001. ISBN 3-8047-1773-X （德语）.

[pmid1107462-5] Murray MA, Bancroft JH, Anderson DC, Tennent TG, Carr PJ. Endocrine changes in male sexual deviants after treatment with anti-androgens, oestrogens or tranquillizers. The Journal of Endocrinology. November 1975, 67 (2): 179–88. PMID 1107462. doi:10.1677/joe.0.0670179.

[6] NCATS Inxight Drugs — BENPERIDOL. [13 March 2022].

[:1-7] 7.0 ^7.1 ^7.2 ^7.3 ^7.4 Li P, Snyder GL, Vanover KE. Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future. Current Topics in Medicinal Chemistry. December 2016, 16 (29): 3385–3403. PMC 5112764  . PMID 27291902. doi:10.2174/1568026616666160608084834.

[:0-8] 8.0 ^8.1 Leucht S, Hartung B. Benperidol for schizophrenia. The Cochrane Database of Systematic Reviews. April 2005, 2005 (2): CD003083. PMC 7017029  . PMID 15846648. doi:10.1002/14651858.CD003083.pub2.

[PDSP-9] Roth BL, Driscol J. PDSP K_i Database. Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. [11 March 2022].

[10] Thieme

[:2-11] BE 626307 (1963 to Janssen), C.A. 60, 10690c (1964), corresp. to GB 989755,“1-(1-aroylpropyl-4-piperidyl)-2-benzimidazolinones and related compounds”,发表于1965-04-22,指定于Janssen Pharmaceuticals#History

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