SIBUTRAMINE MESYLATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H26ClN.CH4O3S
Molecular Weight	375.954
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CS(O)(=O)=O.CC(C)CC(N(C)C)C1(CCC1)C2=CC=C(Cl)C=C2

InChI

InChIKey=MWKDQYLHASOIBB-UHFFFAOYSA-N

InChI=1S/C17H26ClN.CH4O3S/c1-13(2)12-16(19(3)4)17(10-5-11-17)14-6-8-15(18)9-7-14;1-5(2,3)4/h6-9,13,16H,5,10-12H2,1-4H3;1H3,(H,2,3,4)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm

Subitramine is a potent inhibitor of monoamines (serotonin, dopamine, noradrenaline) reuptake that was approved by FDA for the treatmen of obesity. Sibutramine is metabolized to metabolites M1 and M2 which are more active toward the monoamine transporters.The drug was withdrawn from the market because of clinical trial data indicating an increased risk of heart attack and stroke. It was sold under a variety of brand names including Reductil, Meridia and Sibutrex.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sodium-dependent serotonin transporter 40 Target ID: P31645 Gene ID: 6532.0 Gene Symbol: SLC6A4 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	Inhibitor 8297	298.0 nM [Ki]
Sodium-dependent dopamine transporter 42 Target ID: Q01959 Gene ID: 6531.0 Gene Symbol: SLC6A3 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	Inhibitor 8297	943.0 nM [Ki]
Sodium-dependent noradrenaline transporter 38 Target ID: P23975 Gene ID: 6530.0 Gene Symbol: SLC6A2 Target Organism: Homo sapiens (Human) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	Inhibitor 8297	5451.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obesity 203 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	Primary		Withdrawn	MERIDIA Approved Use MERIDIA is indicated for the management of obesity, including weight loss and maintenance of weight loss, and should be used in conjunction with a reduced calorie diet. Launch Date 1997

C_max

Value	Dose	Analyte	Population
4 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
7.12 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15823773/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4067.7 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
6.4 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
8.09 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15823773/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
6579.8 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
4368.5 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	SIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Analyte	Population
25.5 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
133.03 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15823773/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
100736.1 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
92.1 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
205.86 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15823773/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
194500.9 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
23296.9 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	SIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Analyte	Population
22.31 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15823773/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
25.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
17.2 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
23.07 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15823773/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
23.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
3.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29403750/	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	SIBUTRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
6% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		DESMETHYLSIBUTRAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		DIDESMETHYLSIBUTRAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
20 mg 1 times / day multiple, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf Page: 14	unhealthy, adult n = 2068 Health Status: unhealthy Condition: obesity Age Group: adult Sex: unknown Population Size: 2068 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf Page: 14	Disc. AE: Hypertension, Tachycardia... AEs leading to discontinuation/dose reduction: Hypertension (0.4%) Tachycardia (0.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf Page: 14
15 mg 1 times / day multiple, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: multiple Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23444896/	unhealthy, mean 32 years n = 7 Health Status: unhealthy Condition: vasovagal syncope Age Group: mean 32 years Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/23444896/	Disc. AE: Palpitations... Other AEs: Palpitations... AEs leading to discontinuation/dose reduction: Palpitations (1 patient) Other AEs: Palpitations (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/23444896/
20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23444896/	unhealthy, mean 32 years n = 7 Health Status: unhealthy Condition: vasovagal syncope Age Group: mean 32 years Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/23444896/	Other AEs: Palpitations, Paresthesia... Other AEs: Palpitations (1 patient) Paresthesia (1 patient) Anxiety (1 patient) Insomnia (1 patient) Fatigue (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/23444896/
20 mg 1 times / day multiple, oral Studied dose Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	unhealthy, mean 42.9 years n = 146 Health Status: unhealthy Condition: obesity Age Group: mean 42.9 years Sex: M+F Population Size: 146 Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	Disc. AE: Hypertension, Tachycardia... Other AEs: Dry mouth, Anorexia... AEs leading to discontinuation/dose reduction: Hypertension (<1.4%) Tachycardia (<3%) Other AEs: Dry mouth (32.2%) Anorexia (32.2%) Insomnia (10.3%) Increased appetite (11.6%) Nausea (8.2%) Dyspepsia (5.5%) Nervousness (12.3%) Asthenia (8.9%) Dizziness (12.3%) Constipation (12.3%) Rash (4.1%) Palpitation (4.1%) Vasodilation (4.8%) Dyspnea (1.4%) Taste perversion (4.1%) Hypertension (1.4%) Sweating (4.1%) Tachycardia (6.8%) Ecchymosis (1.4%) Paresthesia (3.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	unhealthy, mean 43.3 years n = 203 Health Status: unhealthy Condition: obesity Age Group: mean 43.3 years Sex: M+F Population Size: 203 Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	Disc. AE: Hypertension, Tachycardia... Other AEs: Dry mouth, Anorexia... AEs leading to discontinuation/dose reduction: Hypertension (<2%) Tachycardia (<3%) Other AEs: Dry mouth (16.7%) Anorexia (18.7%) Insomnia (9.4%) Increased appetite (16.7%) Nausea (3.4%) Dyspepsia (4.4%) Nervousness (6.4%) Asthenia (7.9%) Dizziness (7.9%) Constipation (10.8%) Rash (4.9%) Palpitation (4.9%) Vasodilation (2%) Dyspnea (1.5%) Taste perversion (2%) Hypertension (4.9%) Sweating (1%) Tachycardia (4.4%) Ecchymosis (0.5%) Paresthesia (3.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/
30 mg 1 times / day multiple, oral Highest studied dose Dose: 30 mg, 1 times / day Route: oral Route: multiple Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	unhealthy, mean 43.4 years n = 151 Health Status: unhealthy Condition: obesity Age Group: mean 43.4 years Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	Disc. AE: Hypertension, Tachycardia... Other AEs: Dry mouth, Anorexia... AEs leading to discontinuation/dose reduction: Hypertension (2%) Tachycardia (3%) Other AEs: Dry mouth (31.8%) Anorexia (31.8%) Insomnia (24.5%) Increased appetite (21.2%) Nausea (12.6%) Dyspepsia (12.6%) Nervousness (11.3%) Asthenia (10.6%) Dizziness (7.9%) Constipation (7.9%) Rash (7.3%) Palpitation (6%) Vasodilation (5.3%) Dyspnea (4.6%) Taste perversion (4.6%) Hypertension (3.3%) Sweating (2.6%) Tachycardia (2.6%) Ecchymosis (2%) Paresthesia (1.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/
5 mg 1 times / day multiple, oral Minumum effective dose Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	unhealthy, mean 43.4 years n = 169 Health Status: unhealthy Condition: obesity Age Group: mean 43.4 years Sex: M+F Population Size: 169 Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	Disc. AE: Hypertension, Tachycardia... Other AEs: Dry mouth, Anorexia... AEs leading to discontinuation/dose reduction: Hypertension (<1.2%) Tachycardia (<1.8%) Other AEs: Dry mouth (11.8%) Anorexia (18.9%) Insomnia (8.3%) Increased appetite (16.6%) Nausea (4.1%) Dyspepsia (4.1%) Nervousness (5.3%) Asthenia (7.1%) Dizziness (8.9%) Constipation (13%) Rash (4.1%) Vasodilation (2.4%) Dyspnea (0.6%) Taste perversion (1.2%) Hypertension (1.2%) Sweating (1.2%) Tachycardia (1.8%) Ecchymosis (1.2%) Paresthesia (2.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/
15 mg 1 times / day multiple, oral Recommended Dose: 15 mg, 1 times / day Route: oral Route: multiple Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	unhealthy, mean 44.2 years n = 196 Health Status: unhealthy Condition: obesity Age Group: mean 44.2 years Sex: M+F Population Size: 196 Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	Disc. AE: Hypertension, Tachycardia... Other AEs: Dizziness, Dry mouth... AEs leading to discontinuation/dose reduction: Hypertension (<2%) Tachycardia (<3%) Other AEs: Dizziness (8.2%) Dry mouth (25.5%) Anorexia (21.4%) Insomnia (10.2%) Increased appetite (14.3%) Nausea (5.1%) Dyspepsia (8.2%) Nervousness (7.7%) Asthenia (6.1%) Constipation (11.7%) Rash (7.1%) Palpitation (2.6%) Vasodilation (2%) Dyspnea (1%) Taste perversion (2.6%) Hypertension (5.1%) Sweating (2.6%) Tachycardia (7.7%) Ecchymosis (3.1%) Paresthesia (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/
1 mg 1 times / day multiple, oral Minumum effective dose Dose: 1 mg, 1 times / day Route: oral Route: multiple Dose: 1 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	unhealthy, mean 44.5 years n = 149 Health Status: unhealthy Condition: obesity Age Group: mean 44.5 years Sex: M+F Population Size: 149 Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/	Disc. AE: Hypertension, Tachycardia... Other AEs: Dry mouth, Anorexia... AEs leading to discontinuation/dose reduction: Hypertension (<2%) Tachycardia (<0.7%) Other AEs: Dry mouth (6%) Anorexia (20.1%) Insomnia (12.1%) Increased appetite (11.4%) Nausea (3.4%) Dyspepsia (4%) Nervousness (4.7%) Asthenia (2.7%) Dizziness (4.7%) Constipation (6.7%) Rash (5.4%) Palpitations (2%) Vasodilation (1.3%) Dyspnea (1.3%) Taste perversion (0.7%) Hypertension (2%) Tachycardia (0.7%) Paresthesia (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/10102256/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767 substrate 1037	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A 214 OCT2 647	CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667 CYP3A5 395

Drug as perpetrator

Target	Modality	Activity
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 0.829 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 15.6 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19002438/	yes [IC50 29 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 >50 uM]
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 >50 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 >50 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 >50 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 >50 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 >50 uM]
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23777987/ Page: 5.0	yes [IC50 >50 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	yes
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/18474675/ Page: 5.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf#page=3 Page: 3.0	yes	yes (co-administration study) Comment: Ketoconazole: resulted in moderate increases in AUC and Cmax of 58% and 36% for M1 and of 20% and 19% for M2, respectively; Erythromycin: resulted in small increases in the AUC (less than 14%) for M1 and M2. A small reduction in Cmax for M1 (11%) and a slight increase in Cmax for M2 (10%) were observed. Other tested drugs that are substrates and/or inhibitors of CYP 450 isozymes were tested. Cimetidine: resulted insmall increases in combined (M1 and M2) plasma Cmax (3.4%) and AUC (7.3%); Simvastatin: no significant effect on plasma Cmax and AUC of M2 or M1 and M2 combined. The Cmax (16%) and AUC (12%) of M1 were slightly decreased. Simvastatin slightly decreased sibutramine Cmax (14%) and AUC (21%); Omeprazole: slightly increased plasma Cmax and AUC of M1 and M2 combined (approximately 15%). M2 Cmax and AUC were not significantly affected whereas M1 Cmax (30%) and AUC (40%) were modestly increased. Plasma Cmax (57%) and AUC (67%) of unchanged sibutramine were moderately increased; Olanzapine: Olanzapine had no significant effect on plasma Cmax and AUC of M2 and M1 and M2 combined, or the AUC of M1; Lorazepam: Lorazepam had no significant effect on the pharmacokinetics of sibutramine metabolites M1 and M2. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf#page=3 Page: 3.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/18781376/

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1706	http://www.3bsc.com/index/pro_info.php?id=56247
AA Blocks	AA00JOBX	https://www.aablocks.com/goods/Goods/detail?id=AA00JOBX
Aaron Chemicals	AR00JP3P	http://www.aaronchem.com/84485-00-7
AbMole Bioscience	M5958	http://www.abmole.com/products/sibutramine-hcl.html
Achemtek	0104-018656	http://www.achemtek.com/84485-00-7
Alsachim	1918	http://www.alsachim.com/product-C2844-glo.bal-view.html
Aurora Fine Chemicals LLC	A13.140.569	http://online.aurorafinechemicals.com/info?ID=A13.140.569
BioChemPartner	BCP04098	http://www.biochempartner.com/84485-00-7-BCP04098
BioCrick	BCC5252	http://www.biocrick.com/Sibutramine-hydrochloride-BCC5252.html
Boerchem	BC209342	http://www.boerchem.com/?product_35511.html
Chem Scene	CS-2856	http://www.chemscene.com/84485-00-7.html
ChemMol	30104779	http://www.chemmol.com/chemmol/30104779.html
ChemMol	44008671	http://www.chemmol.com/chemmol/44008671.html
ChemMol	49422609	http://www.chemmol.com/chemmol/49422609.html
ChemMol	97900788	http://www.chemmol.com/chemmol/97900788.html
ChemShuttle	159801	http://www.chemshuttle.com/catalogsearch/result/?q=84485-00-7&cat=
Clearsynth	CS-O-02273	https://www.clearsynth.com/en/CSO02273.html
Clearsynth	CS-O-02319	https://www.clearsynth.com/en/CSO02319.html
Clearsynth	CS-T-84979	https://www.clearsynth.com/en/CST84979.html
LGC Standards	DRE-C16944000	https://www.lgcstandards.com/US/en/p/DRE-C16944000
Lab Network	LN00643799	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00643799
MedChem Express	HY-14469	https://www.medchemexpress.com/Sibutramine-hydrochloride.html
OChem	7531	http://www.ocheminc.com/index.php?act=psearch&pid=494S599
Smolecule	S543171	http://www.smolecule.com/products/s543171
Synblock Inc	AB07665	http://www.synblock.com/product/84485-00-7.html
THE BioTek	bt-283286	https://www.thebiotek.com/product/inhibitors/bt-283286
Tocris	2290	https://www.tocris.com/products/sibutramine-hydrochloride_2290
Yuhao Chemical	LT1280	http://www.chemyuhao.com/84485-00-7.html
abcr GmbH	AB376861	http://www.abcr.de/shop/en/AB376861
eNovation Chemicals	D320135	http://www.enovationchem.com/productDetails.asp?productID=D320135

PubMed

Title	Date	PubMed
Dexfenfluramine. An updated review of its therapeutic use in the management of obesity.	1996 Nov	9118819
Sibutramine: a review of the pharmacology of a novel anti-obesity agent.	1997 Mar	9130038
Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from d-amphetamine and d-fenfluramine.	1998 Aug	9758240
Sibutramine: a serotonin-norepinephrine reuptake-inhibitor for the treatment of obesity.	1999 Sep	10492502
[Obesity: principles of drug therapy].	2000 Aug	11026090
An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action.	2000 Oct	12119986
Sibutramine in overweight/obese hypertensive patients.	2001 Dec	11916102
Organic hypomania secondary to sibutramine-citalopram interaction.	2002 Feb	11874219
Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial.	2002 Jan	11840225
Effects of sibutramine on ventricular dimensions and heart valves in obese patients during weight reduction.	2002 Sep	12228789
Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.	2003 Dec	12975638
The effects of sibutramine and orlistat on the ultrasonographic findings, insulin resistance and liver enzyme levels in obese patients with non-alcoholic steatohepatitis.	2003 Sep	14502318
[Pharmacotherapy of obesity].	2004 Oct 7	15532736
Use of sibutramine in obese mexican adolescents: a 6-month, randomized, double-blind, placebo-controlled, parallel-group trial.	2006 May	16861099
Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study.	2007 Apr 17	17404163
Open channel block of A-type, kv4.3, and delayed rectifier K+ channels, Kv1.3 and Kv3.1, by sibutramine.	2007 May	17312186
Myocardial infarction induced by appetite suppressants in Malaysia.	2007 Nov 1	17978302
The endocannabinoid system as a target for obesity treatment.	2008	19046740
[Pharmacological therapy of obesity].	2008 Apr	18773755
Sibutramine: current status as an anti-obesity drug and its future perspectives.	2008 Aug	18671470
Sibutramine-induced acute myocardial infarction in a young lady.	2008 Nov	18788006
The use of sibutramine in the management of obesity and related disorders: an update.	2009	19475780
Pharmacotherapy for obesity.	2009 Dec	20002075
Long-term effects of weight-reducing drugs in hypertensive patients.	2009 Jul 8	19588440
Sibutramine versus continuous positive airway pressure in obese obstructive sleep apnoea patients.	2009 Sep	19357147
Multiple effects of sibutramine on ejaculation and on vas deferens and seminal vesicle contractility.	2009 Sep 15	19482040
Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet.	2010 Apr 15	20188082
Diabesity: therapeutic options.	2010 Jun	20518802
[32-year-old patient with acute myocardial infarction possibly induced by the appetite suppressant sibutramine].	2010 May	20446231
The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease.	2010 May	20415685
Elevation of QT dispersion after obesity drug sibutramine.	2010 Nov	20671571
[Long-term effects of weight-reducing drugs in hypertensive patients--a survey of a Cochrane review].	2011 Feb 21	21333255
Effects of oral anorexiant sibutramine on the expression of cytochromes P450s in human hepatocytes and cancer cell lines.	2013 Dec	24038852
Potent inhibition of cytochrome P450 2B6 by sibutramine in human liver microsomes.	2013 Sep 5	23777987
Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment.	2015 Nov	26259608

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose is 10 mg administered once daily with or without food.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

SIBUTRAMINE MESYLATE

Common Name

English

Sibutramine mesilate [WHO-DD]

Common Name

English

SIBUTRAMINE MESILATE

Common Name

English

CYCLOBUTANEMETHANAMINE, 1-(4-CHLOROPHENYL)-N,N-DIMETHYL-.ALPHA.-(2-METHYLPROPYL)-, METHANESULFONATE (1:1)

Systematic Name

English

SIBUTRAMINE METHANESULFONATE

Common Name

English

Code System Code Type Description

FDA UNII

NTF6Z4MEY2

Created by admin on Sat Dec 16 15:54:56 GMT 2023 , Edited by admin on Sat Dec 16 15:54:56 GMT 2023

PRIMARY

CAS

676598-10-0

Created by admin on Sat Dec 16 15:54:56 GMT 2023 , Edited by admin on Sat Dec 16 15:54:56 GMT 2023

PRIMARY

PUBCHEM

10452134

Created by admin on Sat Dec 16 15:54:56 GMT 2023 , Edited by admin on Sat Dec 16 15:54:56 GMT 2023

PRIMARY

ACTIVE MOIETY


					WV5EC51866

SIBUTRAMINE

SUBSTANCE RECORD


					NTF6Z4MEY2

SIBUTRAMINE MESYLATE

Details

SMILES

InChI

DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdfCurator's Comment: description was created based on several sources, including http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020632s034s035lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm

C_max

T_1/2

F_unbound

Drug as perpetrator