Clocapramine

Clocapramine
Clinical data
Trade names	Clofekton, Padrasen
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral
ATC code	None;
Legal status
Legal status	In general: ℞ (Prescription only);
Identifiers
	IUPAC name 1-[3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)propyl]-4-piperidin-1-ylpiperidine-4-carboxamide;
CAS Number	47739-98-0;
PubChem CID	2793;
DrugBank	DB09003 ;
ChemSpider	2691;
UNII	6EEL1GB72K;
KEGG	D07718;
ChEMBL	ChEMBL2104103;
CompTox Dashboard (EPA)	DTXSID1057749 ;
Chemical and physical data
Formula	C28H37ClN4O
Molar mass	481.08 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Clc1ccc3c(c1)N(c2ccccc2CC3)CCCN5CCC(C(=O)N)(N4CCCCC4)CC5;

Clocapramine (Clofekton, Padrasen), also known as 3-chlorocarpipramine, is an atypical antipsychotic of the iminostilbene class which was introduced in Japan in 1974 by Yoshitomi for the treatment of schizophrenia.^[1]^[2]^[3]^[4]^[5] In addition to psychosis, clocapramine has also been used to augment antidepressants in the treatment of anxiety and panic.^[6]

Clocapramine has been reported to act as an antagonist of the D₂, 5-HT_2A, α₁-adrenergic, and α₂-adrenergic receptors, and does not inhibit the reuptake of either serotonin or norepinephrine.^[4]^[7]^[8]^[9]^[10] It has also been shown to have affinity for SIGMAR1.^[11] Clocapramine's affinity for the 5-HT_2A receptor is greater than that for the D₂ receptor and it has a lower propensity for inducing extrapyramidal symptoms compared to typical antipsychotics, thus underlying its atypical nature.^[4]^[5]^[10]

Clinical trials

In several clinical trials, clocapramine has been compared to other neuroleptic agents. Against haloperidol, though there was no significant difference in efficacy at the end of the study, clocapramine tended to be superior in alleviating motor retardation, alogia, and thought disorder, and also produced fewer side effects.^[12] Against sulpiride, clocapramine demonstrated more favorable effects in the treatment of both positive and negative symptoms, including motor retardation, delusions, hallucinations, and social isolation, though it produced more side effects.^[13] Against timiperone, clocapramine showed lower efficacy against both positive and negative symptoms and produced more side effects such as dyskinesia, insomnia, constipation, and nausea.^[14]

Clocapramine has been implicated in at least one fatality, a suicide in which there were two self-inflicted stab wounds and an overdose of clocapramine as well as three other antipsychotics was taken.^[15] The stab wounds could not explain the death, and thus, it was attributed to multiple drug toxicity instead.^[15]

References

^ David J. Triggle (1997). Dictionary of pharmacological agents. London: Chapman & Hall. ISBN 978-0-412-46630-4.
^ Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. p. 1932. ISBN 978-3-88763-075-1.
^ Sittig, Marshall (1988). Pharmaceutical manufacturing encyclopedia. Park Ridge, N.J., U.S.A: Noyes Publications. pp. 1756. ISBN 978-0-8155-1144-1. clocapramine.
^ ^a ^b ^c Sumiyoshi T, Suzuki K, Sakamoto H, et al. (February 1995). "Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy". Neuropsychopharmacology. 12 (1): 57–64. doi:10.1016/0893-133X(94)00064-7. PMID 7766287.
^ ^a ^b Oka T, Hamamura T, Lee Y, et al. (November 2004). "Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain". Life Sciences. 76 (2): 225–37. doi:10.1016/j.lfs.2004.08.009. PMID 15519367.
^ Saito M, Miyaoka H (August 2007). "Augmentation of paroxetine with clocapramine in panic disorder". Psychiatry and Clinical Neurosciences. 61 (4): 449. doi:10.1111/j.1440-1819.2007.01690.x. PMID 17610675. S2CID 38739899.
^ Kurihara M, Tsumagari T, Setoguchi M, Fukuda T (1982). "A study on the pharmacological and biochemical profile of clocapramine". International Pharmacopsychiatry. 17 (2): 73–90. doi:10.1159/000468561. PMID 6125486.
^ Tsukamoto T, Asakura M, Hirata N, Imafuku J, Matsui H, Hasegawa K (September 1984). "Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action". Biological Psychiatry. 19 (9): 1283–91. PMID 6149771.
^ Setoguchi M, Sakamori M, Takehara S, Fukuda T (June 1985). "Effects of iminodibenzyl antipsychotic drugs on cerebral dopamine and alpha-adrenergic receptors". European Journal of Pharmacology. 112 (3): 313–22. doi:10.1016/0014-2999(85)90776-9. PMID 2862053.
^ ^a ^b Schotte A, Bonaventure P, Janssen PF, Leysen JE (December 1995). "In vitro receptor binding and in vivo receptor occupancy in rat and guinea pig brain: risperidone compared with antipsychotics hitherto used". Japanese Journal of Pharmacology. 69 (4): 399–412. doi:10.1254/jjp.69.399. PMID 8786644.
^ Morio Y, Tanimoto H, Yakushiji T, Morimoto Y (February 1994). "Characterization of the currents induced by sigma ligands in NCB20 neuroblastoma cells". Brain Research. 637 (1–2): 190–6. doi:10.1016/0006-8993(94)91232-7. PMID 7910100. S2CID 19250949.
^ Yamagami S (1985). "A crossover study of clocapramine and haloperidol in chronic schizophrenia". The Journal of International Medical Research. 13 (6): 301–10. doi:10.1177/030006058501300601. PMID 4076529. S2CID 16157745.
^ Yamagami S, Kiriike N, Kawaguchi K (1988). "A single-blind study of clocapramine and sulpiride in hospitalized chronic schizophrenic patients". Drugs Under Experimental and Clinical Research. 14 (11): 707–13. PMID 3246215.
^ Nakazawa T, Ohara K, Sawa Y, et al. (1983). "Comparison of efficacy of timiperone, a new butyrophenone derivative, and clocapramine in schizophrenia: a multiclinic double-blind study". The Journal of International Medical Research. 11 (5): 247–58. doi:10.1177/030006058301100501. PMID 6139317. S2CID 25624985.
^ ^a ^b Koreeda A, Yonemitsu K, Ng'walali PM, Muraoka N, Tsunenari S (October 2001). "Clocapramine-related fatality. Postmortem drug levels in multiple psychoactive drug poisoning". Forensic Science International. 122 (1): 48–51. doi:10.1016/S0379-0738(01)00442-X. PMID 11587865.

[isbn0-412-46630-9-1] David J. Triggle (1997). Dictionary of pharmacological agents. London: Chapman & Hall. ISBN 978-0-412-46630-4.

[isbn3-88763-075-0-2] Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. p. 1932. ISBN 978-3-88763-075-1.

[isbn0-8155-1144-2-3] Sittig, Marshall (1988). Pharmaceutical manufacturing encyclopedia. Park Ridge, N.J., U.S.A: Noyes Publications. pp. 1756. ISBN 978-0-8155-1144-1. clocapramine.

[pmid7766287-4] Sumiyoshi T, Suzuki K, Sakamoto H, et al. (February 1995). "Atypicality of several antipsychotics on the basis of in vivo dopamine-D2 and serotonin-5HT2 receptor occupancy". Neuropsychopharmacology. 12 (1): 57–64. doi:10.1016/0893-133X(94)00064-7. PMID 7766287.

[pmid15519367-5] Oka T, Hamamura T, Lee Y, et al. (November 2004). "Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain". Life Sciences. 76 (2): 225–37. doi:10.1016/j.lfs.2004.08.009. PMID 15519367.

[pmid17610675-6] Saito M, Miyaoka H (August 2007). "Augmentation of paroxetine with clocapramine in panic disorder". Psychiatry and Clinical Neurosciences. 61 (4): 449. doi:10.1111/j.1440-1819.2007.01690.x. PMID 17610675. S2CID 38739899.

[pmid6125486-7] Kurihara M, Tsumagari T, Setoguchi M, Fukuda T (1982). "A study on the pharmacological and biochemical profile of clocapramine". International Pharmacopsychiatry. 17 (2): 73–90. doi:10.1159/000468561. PMID 6125486.

[pmid6149771-8] Tsukamoto T, Asakura M, Hirata N, Imafuku J, Matsui H, Hasegawa K (September 1984). "Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action". Biological Psychiatry. 19 (9): 1283–91. PMID 6149771.

[pmid2862053-9] Setoguchi M, Sakamori M, Takehara S, Fukuda T (June 1985). "Effects of iminodibenzyl antipsychotic drugs on cerebral dopamine and alpha-adrenergic receptors". European Journal of Pharmacology. 112 (3): 313–22. doi:10.1016/0014-2999(85)90776-9. PMID 2862053.

[pmid8786644-10] Schotte A, Bonaventure P, Janssen PF, Leysen JE (December 1995). "In vitro receptor binding and in vivo receptor occupancy in rat and guinea pig brain: risperidone compared with antipsychotics hitherto used". Japanese Journal of Pharmacology. 69 (4): 399–412. doi:10.1254/jjp.69.399. PMID 8786644.

[pmid7910100-11] Morio Y, Tanimoto H, Yakushiji T, Morimoto Y (February 1994). "Characterization of the currents induced by sigma ligands in NCB20 neuroblastoma cells". Brain Research. 637 (1–2): 190–6. doi:10.1016/0006-8993(94)91232-7. PMID 7910100. S2CID 19250949.

[pmid4076529-12] Yamagami S (1985). "A crossover study of clocapramine and haloperidol in chronic schizophrenia". The Journal of International Medical Research. 13 (6): 301–10. doi:10.1177/030006058501300601. PMID 4076529. S2CID 16157745.

[pmid3246215-13] Yamagami S, Kiriike N, Kawaguchi K (1988). "A single-blind study of clocapramine and sulpiride in hospitalized chronic schizophrenic patients". Drugs Under Experimental and Clinical Research. 14 (11): 707–13. PMID 3246215.

[pmid6139317-14] Nakazawa T, Ohara K, Sawa Y, et al. (1983). "Comparison of efficacy of timiperone, a new butyrophenone derivative, and clocapramine in schizophrenia: a multiclinic double-blind study". The Journal of International Medical Research. 11 (5): 247–58. doi:10.1177/030006058301100501. PMID 6139317. S2CID 25624985.

[pmid11587865-15] Koreeda A, Yonemitsu K, Ng'walali PM, Muraoka N, Tsunenari S (October 2001). "Clocapramine-related fatality. Postmortem drug levels in multiple psychoactive drug poisoning". Forensic Science International. 122 (1): 48–51. doi:10.1016/S0379-0738(01)00442-X. PMID 11587865.

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Clocapramine

Clinical trials

See also

References

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