Didesmethylsibutramine

Didesmethylsibutramine

Identifiers
IUPAC name 1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutan-1-amine
CAS Number	84467-54-9  Y
PubChem CID	134772
ChemSpider	118777
UNII	987R943R3P
CompTox Dashboard (EPA)	DTXSID801004734
ECHA InfoCard	100.125.498
Chemical and physical data
Formula	C15H22ClN
Molar mass	251.80 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)CC(C1(CCC1)C2=CC=C(C=C2)Cl)N
InChI InChI=1S/C15H22ClN/c1-11(2)10-14(17)15(8-3-9-15)12-4-6-13(16)7-5-12/h4-7,11,14H,3,8-10,17H2,1-2H3 Key:WQSACWZKKZPCHN-UHFFFAOYSA-N

Didesmethylsibutramine (also known as dinorsibutramine , bisnorsibutramine, and BTS-54524) is an active metabolite of the anorectic drug sibutramine that has been identified as an adulterant in weight loss supplements. ^{[1] [2]} Data on the activity of didesmethylsibutramine in humans is limited, although a case of psychosis associated with didesmethylsibutramine use was reported in 2019. ^[3]

Pharmacology

MAT Affinity (K_i nM) ^[4]

	SERT Tooltip Serotonin transporter	NET Tooltip Norepinephrine transporter	DAT Tooltip Dopamine transporter
Racemate	20	15	45
(R)	140	13	8.9
(S)	4,300	62	12

Didesmethylsibutramine acts as a triple reuptake inhibitor, blocking the reabsorption of serotonin, dopamine, and norepinephrine from neuronal synapses. ^[5] The (R)-enantiomer of didesmethylsibutramine is a more potent inhibitor of monoamine reuptake than the (S)-enantiomer and possesses significantly stronger anorectic activity in animals. ^[6]

Pharmacokinetics

Following sibutramine administration in humans, didesmethylsibutramine (M2) is formed through the N-demethylation of desmethylsibutramine (M1) by CYP2B6. ^[7] Elevated plasma levels of sibutramine are observed with concomitant use of CYP2B6 inhibitors (e.g. clopidogrel) and in individuals with certain CYP2B6 genotypes due to the reduced conversion of sibutramine into desmethylsibutramine. ^{[8] [9]}

See also

• Chlorosipentramine

References

1. Kozhuharov VR, Ivanov K, Ivanova S (22 April 2022). "Dietary Supplements as Source of Unintentional Doping". BioMed Research International. 2022: 8387271. doi: 10.1155/2022/8387271 . PMC   9054437 . PMID   35496041.
2. Kim HJ, Lee JH, Park HJ, Cho SH, Cho S, Kim WS (4 May 2014). "Monitoring of 29 weight loss compounds in foods and dietary supplements by LC-MS/MS". Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment. 31 (5): 777–783. doi:10.1080/19440049.2014.888497. PMID   24499058. S2CID   31818942.
3. Kim MD, Seo JS, Jon DI, Lee KH, Bahk WM, Kwon YJ (9 April 2019). "T64. Two Cases of Brief Affective Psychosis Induced by Diet Aids". Schizophrenia Bulletin. 45 (Supplement_2): S228 –S229. doi: 10.1093/schbul/sbz019.344 . PMC   6455467 .
4. Rothman RB, Baumann MH (May 2009). "Serotonergic drugs and valvular heart disease". Expert Opinion on Drug Safety. 8 (3): 317–329. doi:10.1517/14740330902931524. PMC   2695569 . PMID   19505264.
5. Nisoli E, Carruba MO (October 2000). "An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action". Obesity Reviews. 1 (2): 127–139. doi:10.1046/j.1467-789x.2000.00020.x. PMID   12119986. S2CID   20553857.
6. Glick SD, Haskew RE, Maisonneuve IM, Carlson JN, Jerussi TP (May 2000). "Enantioselective behavioral effects of sibutramine metabolites". European Journal of Pharmacology. 397 (1): 93–102. doi:10.1016/S0014-2999(00)00216-8. PMID   10844103.
7. Bae SK, Cao S, Seo KA, Kim H, Kim MJ, Shon JH, et al. (August 2008). "Cytochrome P450 2B6 catalyzes the formation of pharmacologically active sibutramine (N-{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}-N,N-dimethylamine) metabolites in human liver microsomes". Drug Metabolism and Disposition. 36 (8): 1679–1688. doi:10.1124/dmd.108.020727. PMID   18474675. S2CID   206495548.
8. Bae JW, Jang CG, Lee SY (December 2011). "Effects of clopidogrel on the pharmacokinetics of sibutramine and its active metabolites". Journal of Clinical Pharmacology. 51 (12): 1704–1711. doi:10.1177/0091270010388651. PMID   21209232. S2CID   121878.
9. Pan W, Bae SK, Shim EJ, Park SE, Lee SS, Park SJ, et al. (February 2013). "Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in relation to CYP2B6*6 polymorphism". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 43 (2): 211–218. doi:10.3109/00498254.2012.706722. PMID   22830954. S2CID   25985390.