Klomipramin

Klomipramin
IUPAC ime
	3-(3-hloro-10,11-dihidro-5H-dibenzo[b,f]azepin-5-il)-N,N-dimetilpropan-1-amin
Klinički podaci
Prodajno ime	Anafranil
Drugs.com	Monografija
MedlinePlus	a697002
Kategorija trudnoće	C (U.S.);
Način primene	Oralno, IM, IV
Pravni status
Pravni status	℞ (Prescription only);
Farmakokinetički podaci
Bioraspoloživost	Oralno ~50%
Metabolizam	Hepatički
Poluvreme eliminacije	Klomipramin ~35 sata ; Desmetilklomipramin (glavni aktivni metabolit) ~50 sata
Izlučivanje	Renalno
Identifikatori
CAS broj	303-49-1
ATC kod	N06AA04 (WHO)
PubChem	CID 2801
IUPHAR/BPS	2398
DrugBank	DB01242
ChemSpider	2699
UNII	NUV44L116D
KEGG	D07727
ChEBI	CHEBI:47780
ChEMBL	CHEMBL415
Hemijski podaci
Formula	C19H23ClN2
Molarna masa	314,9 g/mol
	SMILES Clc1ccc3c(c1)N(c2ccccc2CC3)CCCN(C)C; ;
	InChI InChI=1S/C19H23ClN2/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3 ; Key:GDLIGKIOYRNHDA-UHFFFAOYSA-N ;

Klomipramin (Anafranil) je triciklični antidepresiv (TCA). On je razvijen tokom 1960-tih i od tog vremena je u kliničkoj upotrebi širom sveta.^[2]^[3]^[4]^[5]

Farmakologija

Klomipramin je blokator sledećih transportera:^[6]

Serotoninski transporter (SERT) (K_i = 0.14 nM)
Norepinefrinski transporter (NET) (K_i = 54 nM)
Dopaminski transporter (DAT) (K_i = 3,020 nM)
Glicinski transporter (GlyT/LeuT)

On je antagonist/inverzni agonist sledećih receptora:^[6]^[7]^[8]^[9]

5-HT_2A receptor (K_i = 36 nM)
5-HT_2C receptor (K_i = 65 nM)
5-HT₃ receptor (K_i = 85 nM)
5-HT₆ receptor (K_i = 54 nM)
5-HT₇ receptor (K_i = 127 nM)
α₁-adrenergički receptor (K_i = 3.2 nM)
α₂-adrenergički receptor (K_i = 525 nM)
H₁ receptor (K_i = 31 nM)
mACh receptors (K_i = 37 nM)

Aktivni metabolit klomipramina, desmetilklomipramin ispoljava sledeći afinitet:

Norepinefrinski transporter (NET) (K_i = <1 nM)^[10]

Vidi još

Triciklični antidepresivi

Reference

^ DailyMed: About DailyMed
^ Lemke, T.L., Williams, D.A., Roche, V.T., & Zito, S.W., 2012. Foye's Principles of Medicinal Chemistry. 7th ed. Baltimore, MD: Lippincott Williams & Wilkins, p. 605.
^ Healy, D. (2004). Let them eat Prozac: The unhealthy relationship between the pharmaceutical industry and depression. New York: New York University Press, p. 23.
^ Beaumont, G., & Healy, D. (1993). The place of clomipramine in the development of psychopharmacology. Journal of Psychopharmacology, 7, 383–393.
^ Pichot, P. (1996). The discovery of chlorpromazine and the place of psychopharmacology in the history of psychiatry. The Psychopharmacologists (Vol. 1, pp. 1–21). London, England: Chapman & Hall.
^ ^а ^б Millan, M. J.; Gobert, A.; F, Lejeune; et al. (2001). „S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine”. The Journal of Pharmacology and Experimental Therapeutics. 298 (2): 565—80. PMID 11454918.
^ Monsma FJ, Shen Y, Ward RP, Hamblin MW, Sibley DR (1993). „Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs”. Molecular Pharmacology. 43 (3): 320—7. PMID 7680751.
^ Ruat, M.; E, Traiffort; Leurs, R.; et al. (1993). „Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation”. Proceedings of the National Academy of Sciences of the United States of America. 90 (18): 8547—51. PMC 47394 . PMID 8397408. doi:10.1073/pnas.90.18.8547.
^ Toll, L.; Berzetei-Gurske IP; Polgar, W. E.; et al. (1998). „Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications”. NIDA Research Monograph. 178: 440—66. PMID 9686407.
^ P K Gillman (2007). „Tricyclic antidepressant pharmacology and therapeutic drug interactions updated”. Br J Pharmacol. 151 (6): 737—748. PMC 2014120 . PMID 17471183. doi:10.1038/sj.bjp.0707253.

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[1] DailyMed: About DailyMed

[2] Lemke, T.L., Williams, D.A., Roche, V.T., & Zito, S.W., 2012. Foye's Principles of Medicinal Chemistry. 7th ed. Baltimore, MD: Lippincott Williams & Wilkins, p. 605.

[3] Healy, D. (2004). Let them eat Prozac: The unhealthy relationship between the pharmaceutical industry and depression. New York: New York University Press, p. 23.

[4] Beaumont, G., & Healy, D. (1993). The place of clomipramine in the development of psychopharmacology. Journal of Psychopharmacology, 7, 383–393.

[5] Pichot, P. (1996). The discovery of chlorpromazine and the place of psychopharmacology in the history of psychiatry. The Psychopharmacologists (Vol. 1, pp. 1–21). London, England: Chapman & Hall.

[pmid11454918-6] а ^б Millan, M. J.; Gobert, A.; F, Lejeune; et al. (2001). „S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine”. The Journal of Pharmacology and Experimental Therapeutics. 298 (2): 565—80. PMID 11454918.

[pmid7680751-7] Monsma FJ, Shen Y, Ward RP, Hamblin MW, Sibley DR (1993). „Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs”. Molecular Pharmacology. 43 (3): 320—7. PMID 7680751.

[pmid8397408-8] Ruat, M.; E, Traiffort; Leurs, R.; et al. (1993). „Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation”. Proceedings of the National Academy of Sciences of the United States of America. 90 (18): 8547—51. PMC 47394 . PMID 8397408. doi:10.1073/pnas.90.18.8547.

[pmid9686407-9] Toll, L.; Berzetei-Gurske IP; Polgar, W. E.; et al. (1998). „Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications”. NIDA Research Monograph. 178: 440—66. PMID 9686407.

[pmid17471183-10] P K Gillman (2007). „Tricyclic antidepressant pharmacology and therapeutic drug interactions updated”. Br J Pharmacol. 151 (6): 737—748. PMC 2014120 . PMID 17471183. doi:10.1038/sj.bjp.0707253.

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p r u Modulatori sigma receptora
σ₁	Agonisti: 3-PPP 4-PPBP 5-MeO-DMT Alazocin (SKF-10047) Amantadin ANAVEX2-73 Arketamin BD-737 BD-1052 Kaptodiam Citalopram CGRP Kloperastin Kokain Kutamezin (SA-4503) Ciklazocin Dehidroepiandrosteron (DHEA) (prasteron) Dehidroepiandrosteron sulfat (DHEA-S) (prasteron sulfat) Dekstralorfan Dekstrometorfan (DXM) Dekstrorfan (DXO) Dimemorfan Dimetiltriptamin (DMT) Ditolilgvanidin (DTG) Donepezil Eliprodil Escitalopram Fabomotizol (afobazol) Fluoksetin Fluvoksamin Ifenprodil Igmesin (JO-1784) IPAB Ketamin L-687384 MDMA (midomafetamin) Memantin Metamfetamin Metoksetamin Metilfenidat Nepinalon Neuropeptid Y Noskapin OPC-14523 Opipramol Pentazocin Pentoksiverin (karbetapentan) PRE-084 Pregnenolon Pregnenolon sulfat Pridopidin Racemetorfan (metorfan) Racemorfan (morfanol) UMB-23 UMB-82 Antagonisti: 3-PPP AC-927 BD-1008 BD-1031 BD-1047 BD-1060 BD-1063 BD-1067 BMY-14802 (BMS-181100) CM-156 Dup-734 E-5842 E-52862 (S1RA) Haloperidol LR-132 LR-172 MS-377 NE-100 NPC-16377 Panamesin (EMD-57455) PD-144418 Pentazocin Progesteron Rimkazol (BW-234U) Sertralin SR-31742A Alosterni modulatori: Fenitoin; Pozitivni: Metilfenilpiracetam SOMCL-668 Nepoznati/nerazvrstani: 3-Metoksidekstralorfan 3-MeO-PCP 4C-T-2 4-IBP 4-IPBS 4-MeO-PCP 5-MeO-DALT 5-MeO-DiPT Amitriptilin Azidopamil Hlorpromazin Klemastin Klomipramin Klorgilin D-Deprenil DiPT DPT Ibogain Imipramin KCR-12-83.1 Nemonaprid Noribogain RHL-033 RS-67,333 RTI-55 Šafran Safinamid Selegilin Spipetijan Trifluoperazin W-18 YKP10A
σ₂	Agonisti: 3-PPP Arketamin BD-1047 BD1063 Ditolilgvanidin (DTG) DKR-1005 DKR-1051 Haloperidol Ifenprodil Ketamin MDMA (midomafetamin) Metamfetamin OPC-14523 Opipramol PB-28 Fenciklidin Siramesin (Lu 28-179) UKH-1114 Antagonisti: AC-927 BD-1008 BD-1067 CM-156 CT-1812 LR-172 MIN-101 Panamesin (EMD-57455) SAS-0132 Nepoznati/nerazvrstani: 3-Metoksidekstralorfan 3-MeO-PCE 4-MeO-PCP 5-MeO-DALT 5-MeO-DiPT Klemastin DiPT DPT Ibogain Nemonaprid Nepinalon Noribogain Pentazocin RS-67,333 Safinamid TMA UMB-23 UMB-82 W-18
Neraz- vrstani	Agonisti: Berberin Etilketazocin Forfit Metafit Nalbufin Naluzotan Tapentadol Tenociklidin Antagonisti: AHD1 AZ66 Lamotrigin Nalokson SM-21 UMB-100 UMB-101 UMB-103 UMB-116 YZ-011 YZ-069 YZ-185 Alosterni modulatori: SKF-83959 Nepoznati/nerazvrstani: 18-Metoksikoronaridin BMY-13980 Butaklamol Karamifen Karvotrolin Hlorfenamin (hlorfeniramin) Hlorpromazin Cinarizin Cinuperon Klocapramin Dezocin EMD-59983 Hipericin (kantarion) Flufenazin Gevotrolin (WY-47384) Mepiramin (pirilamin) Molindon Perfenazin Pimozid Proadifen Prometazin Propranolol Hinidin Remoksiprid SL 82.0715 SR-31747A Tiospiron (BMY-13859) Venlafaksin