Pecazine

Pecazine (INN), also known as mepazine (trade name Pacatal), is a phenothiazine formerly used as a neuroleptic drug or major tranquilizer.

Mepazine
INN: Pecazine

Clinical data
Trade names	Pacatal, Pacatol, Paxital, Lacumin, Nothiazine
Routes of administration	Oral, parenteral
ATC code	None
Legal status
Legal status	BR: Class C1 (Other controlled substances) US: ℞-only (withdrawn, 21 CFR 216.24)
Identifiers
IUPAC name 10-[(1-methylpiperidin-3-yl)methyl]phenothiazine
CAS Number	60-89-9 2975-36-2 (HCl)
PubChem CID	6075
IUPHAR/BPS	9782
ChemSpider	5850
UNII	PH34873A38
KEGG	D02607
ChEBI	CHEBI:135324
ChEMBL	ChEMBL395110
CompTox Dashboard (EPA)	DTXSID2046177
ECHA InfoCard	100.000.446
Chemical and physical data
Formula	C19H22N2S
Molar mass	310.46 g·mol−1
3D model (JSmol)	Interactive image
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

Pecazine was first synthesized in 1953 by Wilhelm Schuler and Otto Nieschulz and was quickly incorporated into psychiatric practice as an ataractic, i.e., a true tranquilizer rather than a hypnotic or depressant. It was considered interchangeable with chlorpromazine, albeit with a different side effect profile, which included less sedation and a lower risk of extrapyramidal symptoms due to its potent parasympatholytic and anticholinergic effect.^[1]

As early as 1958, however, studies reported inferiority to other phenothiazines in the treatment of schizophrenia and questioned its place in the clinic;^[2][3] in 1960, a double-blind, randomized controlled trial found pecazine to be no more effective than placebo.^[4] Subsequent research found that, like the structurally related promethazine, pecazine is essentially devoid of antipsychotic activity.^[5]

Pecazine was implicated in a number of cases of agranulocytosis and was subsequently withdrawn from the market.^[6][7][8][9] More recently, it has become a subject of research interest as a MALT1 and RANKL inhibitor.^[10][11]

References

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