Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMK7F9S)

Drug Name

Amitriptyline Drug Info

Synonyms

Adepress; Adepril; Amitril; Amitriprolidine; Amitriptilina; Amitriptylin; Amitriptylinum; Amitryptiline; Amitryptyline; Amytriptiline; Amytriptylin; Damilan; Damilen; Damitriptyline; Elanil; Elavil; Flavyl; Lantron; Laroxil; Laroxyl; Proheptadiene; Redomex; Sarotex; Seroten; Sylvemid; Triptanol; Triptilin; Triptisol; Tryptanol; Amitriptilina [Italian]; Amitriptylin [German]; MK 230; N 750; TP0; Amitriptilina [INN-Spanish]; Amitriptyline (INN); Amitriptyline [INN:BAN]; Amitriptylinum [INN-Latin]; Elavil (TN); Laroxyl (TN); Ro 4-1575; [3-(10,11-Dihydro-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-dimethyl-amine; 10,11-Dihydro-5-(gamma-dimethylaminopropylidene)-5H-dibenzo(a,d)cycloheptene; 10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-delta(5),gamma-propylamine; 10,11-dihydro-5-(gamma-dimethylaminopropylidene)-5H-dibenzo[a,d]cycloheptene; 3-(10,11-Dihydro-5H-dibenzo(a,d)cyclohepten-5-yliden)-N,N-dimethylpropylamin; 3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N,N-dimethylpropan-1-amine; 5-(3'-Dimethylaminopropylidene)-dibenzo-(a,d)(1,4)-cycloheptadiene; 5-(3'-Dimethylaminopropylidene)-dibenzo-[a,d][1,4]-cycloheptadiene; 5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptatriene; 5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene; 5-(3-Dimethylaminopropylidene)-5H-dibenzo[a,d]-10,11-dihydrocycloheptene; 5-(3-dimethylaminopropylidene)dibenzo[a,d][1,4]-cycloheptadiene; 5-(gamma-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene; 5-(gamma-Dimethylaminopropylidene)-5H-Dibenzo[a,d][1,4]cycloheptadiene; 5-(gamma-Dimethylaminopropylidene)-5H-dibenzo(a,d)(1,4)cycloheptadiene; 5-(gamma-Dimethylaminopropylidene)-5H-dibenzo[a,d]10,11-dihydrocycloheptene; 5-(gamma-Dimethylaminopropylidine)-5H-dibenzo(a,d)(1,4)cycloheptadiene

Indication

Disease Entry	ICD 11	Status	REF
Depression	6A70-6A7Z	Approved	[1]
Pain	MG30-MG3Z	Approved	[2]
Mixed anxiety and depressive disorder		Investigative	[2]
Sleep disorder, initiating and maintaining sleep		Investigative	[2]

Therapeutic Class

Analgesics

Cross-matching ID

PubChem CID: 2160
ChEBI ID: CHEBI:2666
CAS Number: CAS 50-48-6
TTD Drug ID: DMK7F9S
VARIDT Drug ID: DR00470
INTEDE Drug ID: DR0095
ACDINA Drug ID: D00032

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Inhibitor	[3]
Serotonin transporter (SERT)	TT3ROYC	SC6A4_HUMAN	Inhibitor	[3]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Approved	[5]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Approved	[6]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Approved	[5]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Approved	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Approved	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Approved	[9]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Approved	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Approved	[11]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Approved	[12]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Approved	[13]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Norepinephrine transporter (NET)	DTT	SLC6A2	2.459	3.426	3.322	3.35
Serotonin transporter (SERT)	DTT	SLC6A4	6.278	5.469	6.075	6.966
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Cytochrome P450 2E1 (CYP2E1)	DME	CYP2E1	12.054	3.968	2.945	4.1
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	9.791	3.744	3.413	1.609
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	10.036	5.779	6.508	6.481
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	10.08	7.207	5.403	9.211
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.867	5.142	5.52	7.08
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	3.307	5.005	3.921	5.327
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	11.76	5.931	6.164	9.423
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Depression

ICD Disease Classification

6A70-6A7Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serotonin transporter (SERT)	DTT	SLC6A4	8.76E-01	7.18E-05	6.19E-04
P-glycoprotein 1 (ABCB1)	DTP	P-GP	6.54E-01	1.95E-01	4.04E-01
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DME	UGT1A1	4.53E-01	4.14E-02	1.83E-01
Cytochrome P450 2E1 (CYP2E1)	DME	CYP2E1	9.45E-02	-1.86E-01	-9.83E-01
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	5.57E-01	-7.89E-02	-7.93E-01
Cytochrome P450 2B6 (CYP2B6)	DME	CYP2B6	4.32E-01	4.39E-02	4.30E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	8.46E-01	-6.63E-03	-4.49E-02
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.57E-01	9.43E-03	1.29E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	9.62E-01	2.57E-02	1.10E-01
Cytochrome P450 2D6 (CYP2D6)	DME	CYP2D6	8.70E-01	2.98E-02	1.22E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	2.35E-01	2.78E-02	2.09E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.76E-01	1.26E-01	8.27E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 200).
2	Amitriptyline FDA Label
3	Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
4	Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22.
5	Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67.
6	Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4. J Clin Pharmacol. 1998 Feb;38(2):112-21.
7	Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44.
8	Liquid chromatography-tandem mass spectrometry method for measurement of nicotine N-glucuronide: a marker for human UGT2B10 inhibition. J Pharm Biomed Anal. 2011 Jul 15;55(5):964-71.
9	A study on CYP2C19 and CYP2D6 polymorphic effects on pharmacokinetics and pharmacodynamics of amitriptyline in healthy Koreans. Clin Transl Sci. 2017 Mar;10(2):93-101.
10	The genetic profiles of CYP1A1, CYP1A2 and CYP2E1 enzymes as susceptibility factor in xenobiotic toxicity in Turkish population. Saudi Pharm J. 2017 Feb;25(2):294-297.
11	Effects of cytochrome b(5) on drug oxidation activities of human cytochrome P450 (CYP) 3As: similarity of CYP3A5 with CYP3A4 but not CYP3A7. Biochem Pharmacol. 2003 Dec 15;66(12):2333-40.
12	Application of the relative activity factor approach in scaling from heterologously expressed cytochromes p450 to human liver microsomes: studies on amitriptyline as a model substrate. J Pharmacol Exp Ther. 2001 Apr;297(1):326-37.
13	The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000 Dec;50(6):573-80.