MELATONIN

US Previously Marketed

First marketed in 1921

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H16N2O2
Molecular Weight	232.2783
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(NC=C2CCNC(C)=O)C=C1

InChI

InChIKey=DRLFMBDRBRZALE-UHFFFAOYSA-N

InChI=1S/C13H16N2O2/c1-9(16)14-6-5-10-8-15-13-4-3-11(17-2)7-12(10)13/h3-4,7-8,15H,5-6H2,1-2H3,(H,14,16)

HIDE SMILES / InChI

Molecular Formula	C13H16N2O2
Molecular Weight	232.2783
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26731279 | https://www.ncbi.nlm.nih.gov/pubmed/19966183 |

Melatonin (5-methoxy N-acetyltryptamine) is a hormone synthesized and released from the pineal gland at night, which acts on specific high affinity G-protein coupled receptors to regulate various aspects of physiology and behaviour, including circadian and seasonal responses, and some retinal, cardiovascular and immunological functions. Melatonin is also made synthetically and available without a prescription as an over-the-counter (OTC) dietary supplement in the U.S. Melatonin supplementation has many uses, however, it has been widely studied for treatment of jet lag and sleep disorders. Parents may consider using melatonin to help their child who has a trouble falling asleep. A medical professional should always evaluate insomnia or other sleeping disorders in children. Additionally, melatonin has been shown to protect against oxidative stress in various, highly divergent experimental systems. There are many reasons for its remarkable protective potential. In mammals, melatonin binds to a number of receptor subtypes including high-affinity (MT1 and MT2) and low-affinity (MT3, nuclear orphan receptors) binding sites, which are distributed throughout the central nervous system and periphery.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Melatonin receptor type 1A 3 Target ID: P48039 Gene ID: 4543.0 Gene Symbol: MTNR1A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19966183	Agonist 2752
Melatonin receptor type 1B 4 Target ID: P49286 Gene ID: 4544.0 Gene Symbol: MTNR1B Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19449447	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Jet lag syndrome 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26731279	Primary		Not Provided 511	Unknown Approved Use Unknown
Insomnia 111 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28364493	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
26813 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31004517/	3 mg single, nasogastric dose: 3 mg route of administration: Nasogastric experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
312162.5 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26184078/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1416325 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26184078/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
389875 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26893170/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1465 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36046952/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
240 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/36046952/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
49.474 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
18.294 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
74.59 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
120.804 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
44441 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31004517/	3 mg single, nasogastric dose: 3 mg route of administration: Nasogastric experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
9634812.7 pg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26184078/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
67047375.2 pg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26184078/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
14179767.6 pg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26893170/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4590.6 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1624.6 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5509.8 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9791.6 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
0.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31004517/	3 mg single, nasogastric dose: 3 mg route of administration: Nasogastric experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
42.3 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26184078/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
46.2 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26184078/	100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
39.4 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26893170/	10 mg single, intravenous dose: 10 mg route of administration: Intravenous experiment type: SINGLE co-administered:	MELATONIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
55.168 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
58.854 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
49.374 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
44.454 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24650045/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	MELATONIN serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg single, intravenous Highest studied dose Dose: 100 mg Route: intravenous Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/26184078/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26184078/	Sources: https://pubmed.ncbi.nlm.nih.gov/26184078/
16 mg single, oral Highest studied dose Dose: 16 mg Route: oral Route: single Dose: 16 mg Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf#page=12 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K100_1.pdf#page=23 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K101_1.pdf#page=249	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf#page=12 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K100_1.pdf#page=23 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K101_1.pdf#page=249	Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf#page=12 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K100_1.pdf#page=23 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K101_1.pdf#page=249
4 mg 1 times / day multiple, oral Studied dose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf#page=40 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K100_1.pdf#page=187 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K101_1.pdf#page=97	unhealthy, CHILD Health Status: unhealthy Age Group: CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf#page=40 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K100_1.pdf#page=187 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K101_1.pdf#page=97	Disc. AE: Somnolence... AEs leading to discontinuation/dose reduction: Somnolence (2, 1 pt) Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf#page=40 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K100_1.pdf#page=187 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K101_1.pdf#page=97
80 mg 1 times / hour multiple, oral Highest studied dose Dose: 80 mg, 1 times / hour Route: oral Route: multiple Dose: 80 mg, 1 times / hour Sources: https://pubmed.ncbi.nlm.nih.gov/6493445/	unknown, UNKNOWN Health Status: unknown Age Group: UNKNOWN Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6493445/	Sources: https://pubmed.ncbi.nlm.nih.gov/6493445/

AEs

AE	Significance	Dose	Population
Somnolence	2, 1 pt Disc. AE	4 mg 1 times / day multiple, oral Studied dose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf#page=40 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K100_1.pdf#page=187 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K101_1.pdf#page=97	unhealthy, CHILD Health Status: unhealthy Age Group: CHILD Sex: M+F Food Status: UNKNOWN Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf#page=40 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K100_1.pdf#page=187 https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_K101_1.pdf#page=97

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946 inducer 1087	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2E1 1060 CYP1B1 32 MRP4 290 MRP3 246 CYP2A6 879 CYP2C19 2057 MRP2 499 CYP1A1 132 BSEP 550 OATP1B1 1079 OATP1B3 961 CYP19A1 429 OCT2 779 OAT3 747 P-gp 1741 CYP2C8 1057 OAT1 725 MATE2-K 77 MATE1 415	CYP1B1 104 SULT1A3 31 CYP2E1 729 SULT1B1 8 CYP2B6 776 CYP1A2 1197 SULT1A1 37 BCRP 697 SULT1A2 3 SULT1E1 22 CYP1A1 389 OATP1B3 435 OATP1B1 503 P-gp 2052 CYP4A11 137 CYP2A6 626 CYP2C19 1119	CYP1A2 832 CYP2B6 669

Drug as perpetrator

Target	Modality	Activity
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDUifX0=	inconclusive [IC50 10 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/896#section=Biological-Test-Results Page: 85.0	no [IC50 38.5708 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	no [IC50 >10 uM]
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	no [IC50 >133 uM]
MRP2 625	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1NzQ4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1OTE4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTI4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	no [IC50 >133 uM]
CYP1A2 2333	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
CYP2B6 1160	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
CYP3A4 2633	inducer 1966 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
MATE1 416	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
MATE2-K 77	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
OAT1 730	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
OAT3 749	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
OCT2 782	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
CYP1B1 93	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw0ODc4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	yes [IC50 14 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDUifX0=	yes [IC50 19.9526 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	yes [IC50 5.0119 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	yes [Inhibition 10 uM]
CYP1A1 272	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyMjMxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ1In19	yes [Ki 59 uM]
BCRP 985	supressor 160 Sources: https://pubmed.ncbi.nlm.nih.gov/25738837/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
SULT1A1 37	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27633141/ \| https://pubmed.ncbi.nlm.nih.gov/25738837/	major [Km 1.73 uM]	6-hydroxymelatonin 1
SULT1A2 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27633141/ \| https://pubmed.ncbi.nlm.nih.gov/25738837/	major [Km 1080.71 uM]	6-hydroxymelatonin 1
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	major [Km 19.2 uM]
SULT1A3 31	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27633141/ \| https://pubmed.ncbi.nlm.nih.gov/25738837/	major [Km 198.91 uM]	6-hydroxymelatonin 1
SULT1E1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27633141/ \| https://pubmed.ncbi.nlm.nih.gov/25738837/	major [Km 20.98 uM]	6-hydroxymelatonin 1
SULT1A3 31	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27633141/ \| https://pubmed.ncbi.nlm.nih.gov/25738837/	major [Km 215.73 uM]	N-acetylserotonin 1
SULT1A2 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27633141/ \| https://pubmed.ncbi.nlm.nih.gov/25738837/	major [Km 2392.39 uM]	N-acetylserotonin 1
SULT1E1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27633141/ \| https://pubmed.ncbi.nlm.nih.gov/25738837/	major [Km 248.22 uM]	N-acetylserotonin 1
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/ \| https://pubmed.ncbi.nlm.nih.gov/10877005/	major [Km 25.9 uM]		yes (co-administration study) Comment: Fluvoxamine increased melatonin Cmax by ca. 3-fold. Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/ \| https://pubmed.ncbi.nlm.nih.gov/10877005/
SULT1A1 37	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/27633141/ \| https://pubmed.ncbi.nlm.nih.gov/25738837/	major [Km 27.25 uM]	N-acetylserotonin 1
CYP1B1 104	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	major [Km 30.9 uM]
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/ \| https://pubmed.ncbi.nlm.nih.gov/10877005/	major		yes (co-administration study) Comment: Fluvoxamine increased melatonin Cmax by ca. 3-fold. Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/ \| https://pubmed.ncbi.nlm.nih.gov/10877005/
OATP1B1 503	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
OATP1B3 435	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
P-gp 2052	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	no
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	weak
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	weak
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	weak
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	weak
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	weak
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	weak
CYP4A11 137	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15616152/	weak
SULT1B1 8	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25738837/	yes [Km 1823.15 uM]	6-hydroxymelatonin 1
SULT1B1 8	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25738837/	yes [Km 88.41 uM]	N-acetylserotonin 1
BCRP 697	substrate 4014 Sources: https://www.pmda.go.jp/drugs/2020/P20200408001/620095000_30200AMX00439_A100_1.pdf Page: 21.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMNDUifX0=

PubMed

Title	Date	PubMed
Dual effects of melatonin on barbiturate-induced narcosis in rats.	2001-03-16	11226639
Phenolamine-dependent adenylyl cyclase activation in Drosophila Schneider 2 cells.	2001-03-15	11222942
Melatonin inhibits the expression of steroidogenic acute regulatory protein and steroidogenesis in MA-10 cells.	2001-03-07	11229798
Tissue-specific abolition of Per1 expression in the pars tuberalis by pinealectomy in the Syrian hamster.	2001-03-05	11234767
Disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men.	2001-03	11238497
Circadian rhythms of women with fibromyalgia.	2001-03	11238482
The immunotherapeutic potential of melatonin.	2001-03	11227046
Effect of melatonin on oxidative status of rat brain, liver and kidney tissues under constant light exposure.	2001-03	11223869
Multiple binding sites for melatonin on Kv1.3.	2001-03	11222291
Photoresponsive Fischer 344 Rats are reproductively inhibited by melatonin and differ in 2-[125I] lodomelatonin binding from nonphotoresponsive Sprague-Dawley rats.	2001-03	11207936
Enzymatic characterization and interspecies difference of phenol sulfotransferases, ST1A forms.	2001-03	11181495
The effect of short intermittent light exposures on the melatonin circadian rhythm and NMU-induced breast cancer in female F344/N rats.	2001-02-24	11215676
A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome.	2001-02-24	11211063
Melatonin secretion after surgery.	2001-02-17	11229697
An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.	2001-02-09	11232563
The critical stage of pinealectomy surgery after which scoliosis is produced in young chickens.	2001-02-01	11224858
Pineal modulation of thymus and immune function in a seasonally breeding tropical rodent, Funambulus pennanti.	2001-02-01	11169496
Melatonin's gastroprotective and antistress roles involve both central and peripheral effects.	2001-02	11227676
Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study.	2001-02	11226744
Effects of bilateral ganglionectomy and melatonin replacement on seasonal rhythm of testicular activity in Zembra Island wild rabbits (Oryctolagus cuniculus).	2001-02	11226057
Melatonin as a sedation substitute for diagnostic procedures: MRI and EEG.	2001-02	11221904
Effects of aging on the intrinsic circadian period of totally blind humans.	2001-02	11220783
Low ambient temperature accelerates short-day responses in Siberian hamsters by altering responsiveness to melatonin.	2001-02	11220782
Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy.	2001-02	11207642
Chronic exposure to ELF magnetic fields during night sleep with electric sheet: effects on diurnal melatonin rhythms in men.	2001-02	11180260
The influence of 1.2 microT, 60 Hz magnetic fields on melatonin- and tamoxifen-induced inhibition of MCF-7 cell growth.	2001-02	11180258
Diurnal and seasonal variations in the duration and depth of the longest dives in southern elephant seals (Mirounga leonina): possible physiological and behavioural constraints.	2001-02	11171347
Direct separation of the stereoisomers of methoxytetrahydronaphthalene derivatives, new agonist and antagonist ligands for melatonin receptors, by liquid chromatography on cellulose chiral stationary phases.	2001-01-12	11217017
Effects of melatonin, morphine and diazepam on formalin-induced nociception in mice.	2001-01-12	11213364
Effects by doxorubicin on the myocardium are mediated by oxygen free radicals.	2001-01-12	11213359
Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: association of antiproliferative action of the pineal hormone with mt1 receptor protein expression.	2001-01-01	11170132
Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study.	2001-01	11235927
Interaction between the adrenal and the pineal gland in chronic experimental inflammation induced by BCG in mice.	2001-01	11235023
[Melatonin: is there a rationale for the clinical use of this hormone in sleep therapy?].	2001-01	11233494
[Drug for the treatment of sleep disorders--review].	2001-01	11233487
Human melatonin regulation is not mediated by the three cone photopic visual system.	2001-01	11232036
Transition from dim to bright light in the morning induces an immediate elevation of cortisol levels.	2001-01	11231993
Diminished melatonin secretion in the elderly caused by insufficient environmental illumination.	2001-01	11231989
Circadian phase resetting in older people by ocular bright light exposure.	2001-01	11217145
Superior cervical ganglionectomy leads to dampening of amplitude of temperature rhythm in rats.	2001-01	11211561
An age-related decline in melatonin secretion is not altered by food restriction.	2001-01	11193220
Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study.	2001-01	11180494
Absolute configuration of N-[(-)-2-(7-methoxy-1,2,3,3-tetrahydro-1-naphthyl)ethyl]cyclopropylcarboxamide, a highly potent and selective melatonin analogue.	2001-01	11173413
A test of the coincidence and duration models of melatonin action in Siberian hamsters. II. The effects of 4- and 8-hr melatonin infusions on testicular development of pinealectomized juvenile Siberian hamsters (Phodopus sungorus).	2001-01	11168908
Absence of sexual dimorphism in pars tuberalis [125I]-melatonin binding sites of lambs slaughtered in June and in October.	2001-01	11168907
Seasonal alterations in circadian melatonin rhythms of the European wild boar and domestic gilt.	2001-01	11168906
Lack of changes in serum prolactin, FSH, TSH, and estradiol after melatonin treatment in doses that improve sleep and reduce benzodiazepine consumption in sleep-disturbed, middle-aged, and elderly patients.	2001-01	11168905
Effects of tamoxifen and melatonin on mammary gland cancer induced by N-methyl-N-nitrosourea and by 7,12-dimethylbenz(a)anthracene, respectively, in female Sprague-Dawley rats.	2001	11232869
The antioxidative potential of melatonin in the skin.	2001	11225196
Characterization of the protective effects of melatonin and related indoles against alpha-naphthylisothiocyanate-induced liver injury in rats.	2001	11169730

Patents

Sample Use Guides

In Vivo Use Guide

Fast Release Melatonin (FR MLT): 3mg capsules of melatonin will be used. The dose of FR MLT will be 3 mg for children less than or equal to 20 kg, and 6 mg for children greater than 20 kg. The study medication will be given one hour before bedtime, once daily. Drug: Timed Release Melatonin (TR MLT): 3 mg capsules will be used. The dose of TR MLT will be will be 3 mg for children less than or equal to 20 kg, and 6 mg for children greater than 20 kg. The study medication will be given one hour before bedtime, once daily.

Route of Administration: Oral

In Vitro Use Guide

It was observed that 10-7 M melatonin was considered an optimum concentration and significantly promoted the in vitro development of murine microinjected pronuclear embryos, as indicated by the increased blastocyst rate, hatching blastocyst rate and blastocyst cell number. When these blastocysts were implanted into recipient mice, the pregnancy rate and birth rate were significantly higher than those of the microinjected control, respectively. Mechanistic studies revealed that melatonin treatment reduced reactive oxygen species (ROS) production and cellular apoptosis during in vitro embryo development and improved the quality of the blastocysts. The implantation of quality-improved blastocysts led to elevated pregnancy and birth rates. In conclusion, the results revealed that the anti-oxidative and anti-apoptotic activities of melatonin improved the quality of microinjected pronuclear embryos and subsequently increased both the efficiency of embryo implantation and the birth rate of the pups. Therefore, the melatonin supplementation may provide a novel alternative method for generating large numbers of transgenic mice and this method can probably be used in human-assisted reproduction and genome editing.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:33:43 GMT 2025` Edited by `admin` on `Mon Mar 31 17:33:43 GMT 2025`
Record UNII	JL5DK93RCL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MELATONIN

Official Name

English

CIRCADIN

Preferred Name

English

MELATONIN [JAN]

Common Name

English

MELATONIN [EMA EPAR]

Common Name

English

ACETAMIDE, N-(2-(5-METHOXYINDOL-3-YL)ETHYL)-

Systematic Name

English

REGULIN

Brand Name

English

MELATONIN [USP-RS]

Common Name

English

MELATONINE

Common Name

English

NSC-113928

Code

English

MELATONIN [HSDB]

Common Name

English

MELATONIN [DSC]

Common Name

English

BCI-049

Code

English

Melatonin [WHO-DD]

Common Name

English

MELATONIN [MI]

Common Name

English

MELATONIN [GREEN BOOK]

Common Name

English

J5.258B

Code

English

ACETAMIDE, N-(2-(5-METHOXY-1H-INDOL-3-YL)ETHYL)-

Systematic Name

English

MELATOL

Brand Name

English

MELOVINE

Brand Name

English

NSC-56423

Code

English

5-METHOXY N-ACETYL-TRYPTAMINE

Common Name

English

MELATONIN [MART.]

Common Name

English

MELATONIN [VANDF]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

melatonin