哌卡嗪

甲哌啶嗪
INN：哌卡嗪
臨床資料
商品名（英語：Drug nomenclature）	Pacatal, Pacatol, Paxital, Lacumin, Nothiazine
給藥途徑	口服，腸道外給藥
ATC碼	未分配;
法律規範狀態
法律規範	美：處方藥（℞-only）(已撤回, 21 CFR 216.24);
識別資訊
	IUPAC命名法 10-[(1-methylpiperidin-3-yl)methyl]phenothiazine; ;
CAS號	60-89-9（2975-36-2 (鹽酸鹽)）
PubChem CID	6075;
IUPHAR/BPS	9782;
ChemSpider	5850;
UNII	PH34873A38;
KEGG	D02607;
ChEBI	CHEBI:135324;
ChEMBL	ChEMBL395110;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID2046177 ;
ECHA InfoCard	100.000.446
化學資訊
化學式	C19H22N2S
摩爾質量	310.46 g·mol−1
3D模型（JSmol（英語：JSmol））	交互式圖像;
	SMILES CN1CCCC(C1)CN2C3=CC=CC=C3SC4=CC=CC=C42;
	InChI InChI=1S/C19H22N2S/c1-20-12-6-7-15(13-20)14-21-16-8-2-4-10-18(16)22-19-11-5-3-9-17(19)21/h2-5,8-11,15H,6-7,12-14H2,1H3; Key:CBHCDHNUZWWAPP-UHFFFAOYSA-N;

哌卡嗪（INN：pecazine）又名甲哌啶嗪（英語：mepazine），商品名Pacatal，為MALT1（英語：MALT1）蛋白酶的變構抑制劑，是一種已經淘汰的吩噻嗪類抗精神病藥^[1]。

哌卡嗪最早由Wilhelm Schuler（英語：Wilhelm Schuler）和Otto Nieschulz於1953年合成得到，並迅速被作為鎮靜劑（字面意義上鎮靜劑，非廣義上的安眠藥或抑制劑）應用於精神科實踐當中。儘管哌卡嗪強力的副交感神經抑制作用和抗膽鹼作用導致本身鎮靜效果較弱和錐體外系症狀風險低，但其仍被視作是氯丙嗪的替代品^[2]。

然而早在1958年，就有研究報告稱哌卡嗪治療精神分裂的效果不及其他吩噻嗪類藥物，並對其臨床應用地位提出質疑^[3]^[4]。隨後到了1960年，一項雙盲隨機對照實驗發現哌卡嗪甚至不及安慰劑有效^[5]。後續研究發現，哌卡嗪與其結構類似物異丙嗪一樣，本質上不具備抗精神病活性^[6]。

20世紀50年代，因哌卡嗪與多例顆粒性白血球缺乏症（英語：Agranulocytosis）報告有關，導致其被撤出市場^[7]^[8]^[9]^[10]。進入21世紀後，因其對MALT1（英語：MALT1）蛋白酶和RANKL（破骨細胞分化因子）有抑制作用而重新引起研究者研究興趣^[11]^[12]。

參考文獻

^ 英國藥理學會（英語：British Pharmacological Society）. pecazine. The International Union of Basic and Clinical Pharmacology (IUPHAR) / British Pharmacological Society (BPS) Guide to PHARMACOLOGY.
^ Bowens HA. The ataractic drugs: the present position of chlorpromazine, Frenquel, Pacatal, and reserpine in the psychiatric hospital. Am J Psychiatry. December 1956, 113 (6): 530–9. PMID 13372821. doi:10.1176/ajp.113.6.530.
^ Hutchinson JT, Jacobs EH. The place of pacatal in psychiatry. Postgrad Med J. November 1958, 34 (397): 605–8. PMC 2501585 . PMID 13591077. doi:10.1136/pgmj.34.397.605.
^ Casey JF, Lasky JJ, Klett CJ, Hollister LE. Treatment of schizophrenic reactions with phenothiazine derivatives. A comparative study of chlorpromazine, triflupromazine, mepazine, prochlorperazine, perphenazine, and phenobarbital. Am J Psychiatry. August 1960, 117: 97–105. PMID 13808146. doi:10.1176/ajp.117.2.97.
^ Whittier JR, Klein DF, Levine G, Weiss D. Mepazine (pacatal): clinical trial with placebo control and psychological study. Psychopharmacologia. June 1960, 1 (4): 280–7. PMID 13844495. S2CID 28787741. doi:10.1007/BF00404225.
^ Lassen JB. Inhibition and potentiation of apomorphine-induced hypermotility in rats by neuroleptics. Eur. J. Pharmacol. April 1976, 36 (2): 385–93. PMID 1278230. doi:10.1016/0014-2999(76)90092-3.
^ Biezanek A, Gore CP. Agranulocytosis during treatment with pacatal. Lancet. November 1956, 271 (6952): 1081. PMID 13377680. doi:10.1016/s0140-6736(56)90213-6.
^ Feldman PE, Bertone J, Panthel H. Fatal agranulocytosis during treatment with pacatal. Am J Psychiatry. March 1957, 113 (9): 842–3. PMID 13402978. doi:10.1176/ajp.113.9.842.
^ Drake M, Honey NK. Agranulocytosis during mepazine therapy. Med. J. Aust. November 1957, 44 (20): 726–7. PMID 13492769. S2CID 22232507. doi:10.5694/j.1326-5377.1957.tb60246.x.
^ Sherman S, Baur E, Klahre H, Lever PG. Agranulocytosis after 10(N-methyl-piperdyl-3-methyl)phenothiazine, with recovery. N. Engl. J. Med. February 1958, 258 (6): 287. PMID 13504461. doi:10.1056/NEJM195802062580608.
^ Nagel D, Spranger S, Vincendeau M, Grau M, Raffegerst S, Kloo B, Hlahla D, Neuenschwander M, Peter von Kries J, Hadian K, Dörken B, Lenz P, Lenz G, Schendel DJ, Krappmann D. Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL. Cancer Cell. December 2012, 22 (6): 825–37. PMID 23238017. doi:10.1016/j.ccr.2012.11.002 .
^ Schlauderer F, Lammens K, Nagel D, Vincendeau M, Eitelhuber AC, Verhelst SH, Kling D, Chrusciel A, Ruland J, Krappmann D, Hopfner KP. Structural analysis of phenothiazine derivatives as allosteric inhibitors of the MALT1 paracaspase. Angew. Chem. Int. Ed. Engl. September 2013, 52 (39): 10384–7. PMID 23946259. doi:10.1002/anie.201304290.

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[2] 英國藥理學會（英語：British Pharmacological Society）. pecazine. The International Union of Basic and Clinical Pharmacology (IUPHAR) / British Pharmacological Society (BPS) Guide to PHARMACOLOGY.

[pmid13372821-3] Bowens HA. The ataractic drugs: the present position of chlorpromazine, Frenquel, Pacatal, and reserpine in the psychiatric hospital. Am J Psychiatry. December 1956, 113 (6): 530–9. PMID 13372821. doi:10.1176/ajp.113.6.530.

[pmid13591077-4] Hutchinson JT, Jacobs EH. The place of pacatal in psychiatry. Postgrad Med J. November 1958, 34 (397): 605–8. PMC 2501585 . PMID 13591077. doi:10.1136/pgmj.34.397.605.

[pmid13808146-5] Casey JF, Lasky JJ, Klett CJ, Hollister LE. Treatment of schizophrenic reactions with phenothiazine derivatives. A comparative study of chlorpromazine, triflupromazine, mepazine, prochlorperazine, perphenazine, and phenobarbital. Am J Psychiatry. August 1960, 117: 97–105. PMID 13808146. doi:10.1176/ajp.117.2.97.

[pmid13844495-6] Whittier JR, Klein DF, Levine G, Weiss D. Mepazine (pacatal): clinical trial with placebo control and psychological study. Psychopharmacologia. June 1960, 1 (4): 280–7. PMID 13844495. S2CID 28787741. doi:10.1007/BF00404225.

[pmid1278230-7] Lassen JB. Inhibition and potentiation of apomorphine-induced hypermotility in rats by neuroleptics. Eur. J. Pharmacol. April 1976, 36 (2): 385–93. PMID 1278230. doi:10.1016/0014-2999(76)90092-3.

[pmid13377680-8] Biezanek A, Gore CP. Agranulocytosis during treatment with pacatal. Lancet. November 1956, 271 (6952): 1081. PMID 13377680. doi:10.1016/s0140-6736(56)90213-6.

[pmid13402978-9] Feldman PE, Bertone J, Panthel H. Fatal agranulocytosis during treatment with pacatal. Am J Psychiatry. March 1957, 113 (9): 842–3. PMID 13402978. doi:10.1176/ajp.113.9.842.

[pmid13492769-10] Drake M, Honey NK. Agranulocytosis during mepazine therapy. Med. J. Aust. November 1957, 44 (20): 726–7. PMID 13492769. S2CID 22232507. doi:10.5694/j.1326-5377.1957.tb60246.x.

[pmid13504461-11] Sherman S, Baur E, Klahre H, Lever PG. Agranulocytosis after 10(N-methyl-piperdyl-3-methyl)phenothiazine, with recovery. N. Engl. J. Med. February 1958, 258 (6): 287. PMID 13504461. doi:10.1056/NEJM195802062580608.

[pmid23238017-12] Nagel D, Spranger S, Vincendeau M, Grau M, Raffegerst S, Kloo B, Hlahla D, Neuenschwander M, Peter von Kries J, Hadian K, Dörken B, Lenz P, Lenz G, Schendel DJ, Krappmann D. Pharmacologic inhibition of MALT1 protease by phenothiazines as a therapeutic approach for the treatment of aggressive ABC-DLBCL. Cancer Cell. December 2012, 22 (6): 825–37. PMID 23238017. doi:10.1016/j.ccr.2012.11.002 .

[pmid23946259-13] Schlauderer F, Lammens K, Nagel D, Vincendeau M, Eitelhuber AC, Verhelst SH, Kling D, Chrusciel A, Ruland J, Krappmann D, Hopfner KP. Structural analysis of phenothiazine derivatives as allosteric inhibitors of the MALT1 paracaspase. Angew. Chem. Int. Ed. Engl. September 2013, 52 (39): 10384–7. PMID 23946259. doi:10.1002/anie.201304290.

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