Pecazine Explained
| Drug Name: | Mepazine |
| Inn: | Pecazine |
| Tradename: | Pacatal, Pacatol, Paxital, Lacumin, Nothiazine |
| Routes Of Administration: | Oral, parenteral |
| Atc Prefix: | None |
| Legal Br: | C1 |
| Legal Us: | Rx-only |
| Legal Us Comment: | (withdrawn,) |
| Cas Number: | 60-89-9 |
| Cas Supplemental: | 2975-36-2 (HCl) |
| Pubchem: | 6075 |
| Iuphar Ligand: | 9782 |
| Chemspiderid: | 5850 |
| Unii: | PH34873A38 |
| Kegg: | D02607 |
| Chebi: | 135324 |
| Chembl: | 395110 |
| Iupac Name: | 10-[(1-methylpiperidin-3-yl)methyl]phenothiazine |
| C: | 19 |
| H: | 22 |
| N: | 2 |
| S: | 1 |
| Smiles: | CN1CCCC(C1)CN2C3=CC=CC=C3SC4=CC=CC=C42 |
| Stdinchi: | 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 |
| Stdinchikey: | CBHCDHNUZWWAPP-UHFFFAOYSA-N |
Pecazine (INN), also known as mepazine (trade name Pacatal), is a phenothiazine formerly used as a neuroleptic drug or major tranquilizer.
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Pecazine was implicated in a number of cases of agranulocytosis and was subsequently withdrawn from the market.[6] [7] [8] [9] More recently, it has become a subject of research interest as a MALT1 and RANKL inhibitor.[10] [11]
Notes and References
- Bowens HA . The ataractic drugs: the present position of chlorpromazine, Frenquel, Pacatal, and reserpine in the psychiatric hospital . Am J Psychiatry . 113 . 6 . 530–9 . December 1956 . 13372821 . 10.1176/ajp.113.6.530.
- Hutchinson JT, Jacobs EH . The place of pacatal in psychiatry . Postgrad Med J . 34 . 397 . 605–8 . November 1958 . 13591077 . 2501585 . 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 . 117 . 97–105 . August 1960 . 13808146 . 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 . 1 . 280–7 . June 1960 . 4 . 13844495 . 10.1007/BF00404225. 28787741 .
- Lassen JB . Inhibition and potentiation of apomorphine-induced hypermotility in rats by neuroleptics . Eur. J. Pharmacol. . 36 . 2 . 385–93 . April 1976 . 1278230 . 10.1016/0014-2999(76)90092-3.
- Biezanek A, Gore CP . Agranulocytosis during treatment with pacatal . Lancet . 271 . 6952 . 1081 . November 1956 . 13377680 . 10.1016/s0140-6736(56)90213-6.
- Feldman PE, Bertone J, Panthel H . Fatal agranulocytosis during treatment with pacatal . Am J Psychiatry . 113 . 9 . 842–3 . March 1957 . 13402978 . 10.1176/ajp.113.9.842.
- Drake M, Honey NK . Agranulocytosis during mepazine therapy . Med. J. Aust. . 44 . 20 . 726–7 . November 1957 . 10.5694/j.1326-5377.1957.tb60246.x . 13492769. 22232507 .
- Sherman S, Baur E, Klahre H, Lever PG . Agranulocytosis after 10(N-methyl-piperdyl-3-methyl)phenothiazine, with recovery . N. Engl. J. Med. . 258 . 6 . 287 . February 1958 . 13504461 . 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 . 22 . 6 . 825–37 . December 2012 . 23238017 . 10.1016/j.ccr.2012.11.002. free .
- 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. . 52 . 39 . 10384–7 . September 2013 . 23946259 . 10.1002/anie.201304290.
