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

General Information of Drug (ID: DMUL45H)

• Drug Name: Naltrexone Drug Info
• Synonyms: Depotrex; Naltrel; Vivitrex; Vivitrol; Naltrexone Depot; IBS therapy, Pain Therapeutics; Irritable bowel syndrome therapy, Pain Therapeutics; PTI-901; XR-NTX; Naltrexone (sustained release), DAS; Naltrexone (sustained release), elbion; Naltrexone depot (injectable suspension), DrugAbuse Sciences; Naltrexone depot (injectable suspension), elbion; Opioid antagonists (irritable bowel syndrome), Pain Therapeutics; Naltrexone (low-dose), Pain Therapeutics; Naltrexone (polymer microcapsule depot, opioid addiction/alcohol dependency), Biotek; Naltrexone (transdermal, alcohol/opioid dependence), Syntropharma; Naltrexone (once-monthly controlled-release, Medisorb), Alkermes

Indication

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Approved	[1]
Chronic alcoholism	6C40.2Z	Approved	[2]
Crohn disease	DD70	Approved	[3]
Gastroparesis	DA41.00	Approved	[3]
Inflammatory bowel disease	DD72	Approved	[3]
Obesity	5B81	Approved	[3]
Ulcerative colitis	DD71	Approved	[3]
Human immunodeficiency virus infection	1C62	Phase 4	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]
Chronic pain	MG30	Investigative	[3]

• Cross-matching ID:
  PubChem CID: 5360515
  ChEBI ID: CHEBI:7465
  CAS Number: CAS 16590-41-3
  TTD Drug ID: DMUL45H
  VARIDT Drug ID: DR00968
  INTEDE Drug ID: DR1128
  ACDINA Drug ID: D00455

Molecule-Related Drug Atlas

Drug(s) Targeting Opioid receptor (OPR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methadone	DMTW6IU	Advanced cancer	2A00-2F9Z	Approved	[12]
Ketobemidone	DMM3L6Z	Pain	MG30-MG3Z	Approved	[13]
Oxymorphone	DM65AGJ	Pain	MG30-MG3Z	Approved	[14]
Dextropropoxyphene	DM23HCX	Pain	MG30-MG3Z	Approved	[15]
Sufentanil	DMU7YEL	Analgesia	MB40.8	Approved	[16]
Levorphanol	DMGS80V	Pain	MG30-MG3Z	Approved	[17]
Pentazocine	DM1XBHS	Pain	MG30-MG3Z	Approved	[18]
Nalmefene	DM4YWCZ	Opioid dependence	6C43.2Z	Approved	[19]
Tilidine	DMJW0VS	Pain	MG30-MG3Z	Approved	[20]
Dihydrocodeine	DMB0FWL	Allergic rhinitis	CA08.0	Phase 4	[21]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A1 (UGT1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[22]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[23]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[24]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[25]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[28]
Metronidazole	DMTIVEN	Abscess		Approved	[29]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[30]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[31]

Drug(s) Affected By Nitric oxide synthase, inducible (NOS2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[32]
Indomethacin	DMSC4A7	Bursitis		Approved	[33]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[34]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[35]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[36]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[37]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[38]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[39]
Penicillamine	DM40EF6	Cystinuria	5C60.2	Approved	[40]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[41]

Drug(s) Affected By Follitropin subunit beta (FSHB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[42]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[43]
Goserelin	DMAT8CG	Breast cancer	2C60-2C65	Approved	[44]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[45]
Cetrorelix	DMFD9Q6	Ovarian stimulation	LB45.1	Approved	[46]
Letrozole	DMH07Y3	Estrogen-receptor positive breast cancer		Approved	[47]
Cimetidine	DMH61ZB	Acid-reflux disorder	DA22	Approved	[48]
Risperidone	DMN6DXL	Bipolar I disorder		Approved	[49]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[50]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[51]

Drug(s) Affected By Lutropin subunit beta (LHB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Leuprorelin acetate	DM15HAT	Prostate cancer	2C82.0	Approved	[52]
Levonorgestrel	DM1DP7T	Atypical endometrial hyperplasia		Approved	[53]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[54]
Naloxone	DM3FXMA	Narcotic depression	6A7Z	Approved	[55]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[42]
Alprazolam	DMC7XDN	Anxiety		Approved	[56]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[57]
Norethindrone acetate	DMDGCQP	N. A.	N. A.	Approved	[53]
Metoclopramide	DMFA5MY	Nausea	MD90	Approved	[55]
Cetrorelix	DMFD9Q6	Ovarian stimulation	LB45.1	Approved	[46]

Drug(s) Affected By Mu-type opioid receptor (OPRM1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alvimopan	DMHR8KW	Gastrointestinal disease	DE2Z	Approved	[58]
Fentanyl	DM8WAHT	Analgesia	MB40.8	Approved	[59]
Morphine	DMRMS0L	Advanced cancer	2A00-2F9Z	Approved	[60]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[61]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[62]
Butorphanol	DM5KYPJ	Pain	MG30-MG3Z	Approved	[63]
Oliceridine	DM6MDCF	Acute pain	MG31	Approved	[59]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[64]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[57]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[65]
Alvimopan	DMHR8KW	Gastrointestinal disease	DE2Z	Approved	[58]
Fentanyl	DM8WAHT	Analgesia	MB40.8	Approved	[59]
Morphine	DMRMS0L	Advanced cancer	2A00-2F9Z	Approved	[60]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[61]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[62]
Butorphanol	DM5KYPJ	Pain	MG30-MG3Z	Approved	[63]
Oliceridine	DM6MDCF	Acute pain	MG31	Approved	[59]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[64]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[57]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[65]

Drug(s) Affected By Sodium-dependent dopamine transporter (SLC6A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[66]
Amphetamine	DMSZQAK	Attention deficit hyperactivity disorder	6A05.Z	Approved	[67]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[68]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[69]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[70]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[70]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[57]
Dextroamphetamine	DMMIHVP	Attention deficit hyperactivity disorder	6A05.Z	Approved	[71]
Vorinostat	DMWMPD4	Adult acute monocytic leukemia		Approved	[72]
Permethrin	DMZ0Q1G	Pediculus capitis infestation	1G00.0	Approved	[73]

Drug(s) Affected By Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[74]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[75]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[76]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[32]
Vorinostat	DMWMPD4	Adult acute monocytic leukemia		Approved	[75]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[77]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[78]
SNDX-275	DMH7W9X	Breast cancer	2C60-2C65	Phase 3	[72]
CHLORIDE	DM1TJXA	Solid tumour/cancer	2A00-2F9Z	Phase 3	[79]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[80]

Drug(s) Affected By D(2) dopamine receptor (DRD2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Droperidol	DM0DXA8	Nausea	MD90	Approved	[81]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[81]
Zuclopenthixol	DMKYD5N	Schizophrenia	6A20	Approved	[81]
Meglitinides	DM1OFHN	Type-2 diabetes	5A11	Approved	[82]
Sulpiride	DMF54ZG	Schizophrenia	6A20	Approved	[83]
Risperidone	DMN6DXL	Bipolar I disorder		Approved	[84]
Olanzapine	DMPFN6Y	Bipolar depression		Approved	[85]
Methamphetamine	DMPM4SK	Anxiety		Approved	[86]
Bromocriptine	DMVE3TK	Acromegaly	5A60.0	Approved	[87]
Fluphenazine	DMIT8LX	Psychotic disorder	6A20-6A25	Approved	[88]

Drug(s) Affected By Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flumazenil	DMPCG2L	Benzodiazepine overdose	PC91	Approved	[89]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[90]
DTI-015	DMXZRW0	Brain cancer	2A00	Approved	[91]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[77]
Midazolam	DMXOELT	Agitation	6A70.3	Approved	[92]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[93]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Opioid receptor (OPR)	TTN4QDT	NOUNIPROTAC	Antagonist	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME	DEYGVN4	UD11_HUMAN	Substrate	[7]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Drug Response	[8]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Gene/Protein Processing	[9]
Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6)	OTX4UC3O	GBRA6_HUMAN	Drug Response	[8]
Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2)	OTAOZIGX	GBRB2_HUMAN	Drug Response	[8]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Gene/Protein Processing	[9]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Drug Response	[6]
Nitric oxide synthase, inducible (NOS2)	OTKKIOJ1	NOS2_HUMAN	Gene/Protein Processing	[10]
Sodium-dependent dopamine transporter (SLC6A3)	OT39XG28	SC6A3_HUMAN	Drug Response	[11]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 074918.
• [3] Naltrexone FDA Label
• [4] 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: 1639).
• [5] ClinicalTrials.gov (NCT04365985) Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19. U.S. National Institutes of Health.
• [6] An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44.
• [7] In vivo chronic exposure to heroin or naltrexone selectively inhibits liver microsome formation of estradiol-3-glucuronide in the rat. Biochem Pharmacol. 2008 Sep 1;76(5):672-9.
• [8] Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009 Jul;14(3):328-37.
• [9] Chronic naltrexone treatment induces desensitization of the luteinizing hormone pulse generator for opioid blockade in hyperprolactinemic patients. J Clin Endocrinol Metab. 1995 May;80(5):1739-42. doi: 10.1210/jcem.80.5.7745028.
• [10] Low dose naltrexone therapy in multiple sclerosis. Med Hypotheses. 2005;64(4):721-4.
• [11] Association between the Stin2 VNTR polymorphism of the serotonin transporter gene and treatment outcome in alcohol-dependent patients. Alcohol Alcohol. 2008 Sep-Oct;43(5):516-22. doi: 10.1093/alcalc/agn048. Epub 2008 Jun 14.
• [12] Methadone treatment and its dangers. Medicina (Kaunas). 2009;45(5):419-25.
• [13] The mu1 and mu2 opioid receptor binding of ketobemidone, norketobemidone and 3-dimethylamino-1,1-diphenylbutene. Pharmacol Toxicol. 1996 Aug;79(2):103-4.
• [14] 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: 7094).
• [15] Retrospective diagnosis of an adverse drug reaction in a breastfed neonate: liquid chromatography-tandem mass spectrometry quantification of dextropropoxyphene and norpropoxyphene in newborn and maternal hair. J Anal Toxicol. 2008 Nov-Dec;39(9):787-9.
• [16] mu-opioid receptor-stimulated synthesis of reactive oxygen species is mediated via phospholipase D2. J Neurochem. 2009 Aug;110(4):1288-96.
• [17] Comparison of the effects of dextromethorphan, dextrorphan, and levorphanol on the hypothalamo-pituitary-adrenal axis. J Pharmacol Exp Ther. 2004 May;309(2):515-22.
• [18] Functional characterization of a sigma receptor and its gene expression by haloperidol. Nippon Yakurigaku Zasshi. 1999 Jul;114(1):61-8.
• [19] Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospin... J Pharmacol Exp Ther. 2009 Feb;328(2):588-97.
• [20] Actions of tilidine and nortilidine on cloned opioid receptors. Eur J Pharmacol. 2005 Jan 4;506(3):205-8.
• [21] Affinities of dihydrocodeine and its metabolites to opioid receptors. Pharmacol Toxicol. 2002 Aug;91(2):57-63.
• [22] Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
• [23] Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
• [24] Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
• [25] UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
• [26] Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
• [27] Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
• [28] Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
• [29] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [30] Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
• [31] Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
• [32] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [33] Development of an alternative zebrafish model for drug-induced intestinal toxicity. J Appl Toxicol. 2018 Feb;38(2):259-273. doi: 10.1002/jat.3520. Epub 2017 Oct 13.
• [34] The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice. Exp Eye Res. 2010 Jul;91(1):15-25.
• [35] Gaseous nitrogen oxide promotes human lung cancer cell line A549 migration, invasion, and metastasis via iNOS-mediated MMP-2 production. Toxicol Sci. 2008 Dec;106(2):364-75. doi: 10.1093/toxsci/kfn195. Epub 2008 Sep 16.
• [36] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [37] Mechanism of simvastatin-induced K562 cell apoptosis. Pharmacology. 2009;84(4):191-5. doi: 10.1159/000235907. Epub 2009 Sep 2.
• [38] The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur J Pharmacol. 2007 Feb 28;557(2-3):221-9.
• [39] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [40] D-Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis. Apoptosis. 2012 Oct;17(10):1079-94.
• [41] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [42] Rapid-onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer. Cancer. 2012 Nov 1;118(21):5302-9. doi: 10.1002/cncr.27450. Epub 2012 Apr 4.
• [43] Suppression of spermatogenesis in patients with Beh?et's disease treated with cyclophosphamide and colchicine. Fertil Steril. 1981 Jul;36(1):76-80. doi: 10.1016/s0015-0282(16)45622-0.
• [44] [Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment of moderate-severe endometriosis: a clinical observation]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Nov;34(11):1288-91.
• [45] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [46] Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-suppressed normal men. Exp Clin Endocrinol Diabetes. 1999;107(1):63-9. doi: 10.1055/s-0029-1212075.
• [47] Aromatase inhibition, testosterone, and seizures. Epilepsy Behav. 2004 Apr;5(2):260-3. doi: 10.1016/j.yebeh.2003.12.001.
• [48] Male sexual dysfunction during treatment with cimetidine. Br Med J. 1979 Mar 10;1(6164):659. doi: 10.1136/bmj.1.6164.659.
• [49] Effect of risperidone and olanzapine on reproductive hormones, psychopathology and sexual functioning in male patients with schizophrenia. Psychoneuroendocrinology. 2009 Jan;34(1):129-39. doi: 10.1016/j.psyneuen.2008.08.015. Epub 2008 Oct 5.
• [50] Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex. J Clin Endocrinol Metab. 2000 May;85(5):1918-22. doi: 10.1210/jcem.85.5.6527.
• [51] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [52] Erectile function and nocturnal penile tumescence in patients with prostate cancer undergoing luteinizing hormone-releasing hormone agonist therapy. Int J Urol. 1999 Jan;6(1):19-23. doi: 10.1046/j.1442-2042.1999.06128.x.
• [53] Relative progestational and androgenic activity of four progestins used for male hormonal contraception assessed in vitro in relation to their ability to suppress LH secretion in the castrate male rat. Mol Cell Endocrinol. 2010 Oct 26;328(1-2):16-21. doi: 10.1016/j.mce.2010.06.010. Epub 2010 Jun 25.
• [54] Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard. Arch Toxicol. 2021 Feb;95(2):727-747. doi: 10.1007/s00204-020-02946-5. Epub 2021 Jan 25.
• [55] Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states. J Clin Endocrinol Metab. 1987 Mar;64(3):508-12. doi: 10.1210/jcem-64-3-508.
• [56] The effect of alprazolam on serum cortisol and luteinizing hormone pulsatility in normal women and in women with stress-related anovulation. J Clin Endocrinol Metab. 1995 Mar;80(3):818-23. doi: 10.1210/jcem.80.3.7883836.
• [57] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [58] The in vitro pharmacology of the peripherally restricted opioid receptor antagonists, alvimopan, ADL 08-0011 and methylnaltrexone. Naunyn Schmiedebergs Arch Pharmacol. 2007 May;375(3):205-20. doi: 10.1007/s00210-007-0146-x. Epub 2007 Mar 6.
• [59] A G protein-biased ligand at the ?-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J Pharmacol Exp Ther. 2013 Mar;344(3):708-17.
• [60] Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clin Pharmacol Ther. 2008 Apr;83(4):559-66.
• [61] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [62] The effect of mitragynine on cAMP formation and mRNA expression of mu-opioid receptors mediated by chronic morphine treatment in SK-N-SH neuroblastoma cell. J Ethnopharmacol. 2013 Jun 21;148(1):135-43. doi: 10.1016/j.jep.2013.03.078. Epub 2013 Apr 19.
• [63] In vitro functional characterization of a panel of non-fentanyl opioid new psychoactive substances. Arch Toxicol. 2020 Nov;94(11):3819-3830. doi: 10.1007/s00204-020-02855-7. Epub 2020 Jul 31.
• [64] Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. Mol Pharmacol. 2006 Apr;69(4):1486-91. doi: 10.1124/mol.105.018325. Epub 2006 Jan 24.
• [65] Regulation of opioid and cannabinoid receptor genes in human neuroblastoma and T cells by the epigenetic modifiers trichostatin A and 5-aza-2'-deoxycytidine. Neuroimmunomodulation. 2012;19(3):180-6. doi: 10.1159/000331474. Epub 2012 Jan 18.
• [66] Functional characterization of N-octyl 4-methylamphetamine variants and related bivalent compounds at the dopamine and serotonin transporters using Ca(2+) channels as sensors. Toxicol Appl Pharmacol. 2021 May 15;419:115513. doi: 10.1016/j.taap.2021.115513. Epub 2021 Mar 27.
• [67] Dopamine transporter gene associated with diminished subjective response to amphetamine. Neuropsychopharmacology. 2005 Mar;30(3):602-9. doi: 10.1038/sj.npp.1300637.
• [68] Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells. J Biol Chem. 2016 Oct 14;291(42):22053-22062. doi: 10.1074/jbc.M116.749119. Epub 2016 Aug 23.
• [69] Evaluation of first generation synthetic cannabinoids on binding at non-cannabinoid receptors and in a battery of in?vivo assays in mice. Neuropharmacology. 2016 Nov;110(Pt A):143-153. doi: 10.1016/j.neuropharm.2016.07.016. Epub 2016 Jul 20.
• [70] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [71] Pharmacological characterization of the aminorex analogs 4-MAR, 4,4'-DMAR, and 3,4-DMAR. Neurotoxicology. 2019 May;72:95-100. doi: 10.1016/j.neuro.2019.02.011. Epub 2019 Feb 15.
• [72] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [73] Pyrethroid pesticide-induced alterations in dopamine transporter function. Toxicol Appl Pharmacol. 2006 Mar 15;211(3):188-97. doi: 10.1016/j.taap.2005.06.003. Epub 2005 Jul 11.
• [74] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [75] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [76] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [77] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [78] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [79] A novel allosteric modulatory site on the GABAA receptor beta subunit. Neuron. 1994 Apr;12(4):775-82. doi: 10.1016/0896-6273(94)90330-1.
• [80] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [81] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [82] Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology (Berl). 2008 Apr;197(2):229-35. doi: 10.1007/s00213-007-1029-z. Epub 2007 Dec 6.
• [83] Positron emission tomography measurement of dopamine D? receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. J Clin Psychiatry. 2010 Sep;71(9):1131-7. doi: 10.4088/JCP.08m04307yel. Epub 2010 Feb 23.
• [84] Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents. Pharmacogenet Genomics. 2009 May;19(5):373-82. doi: 10.1097/FPC.0b013e328329a60f.
• [85] Dopamine receptor D2 gene is associated with weight gain in schizophrenic patients under long-term atypical antipsychotic treatment. Pharmacogenet Genomics. 2010 Jun;20(6):359-66. doi: 10.1097/FPC.0b013e3283397d06.
• [86] A preliminary study: novelty seeking, frontal executive function, and dopamine receptor (D2) TaqI A gene polymorphism in patients with methamphetamine dependence. Compr Psychiatry. 2008 Jul-Aug;49(4):387-92. doi: 10.1016/j.comppsych.2008.01.008. Epub 2008 Mar 21.
• [87] Imaging gene-substance interactions: the effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward. Neurosci Lett. 2006 Sep 25;405(3):196-201. doi: 10.1016/j.neulet.2006.07.030. Epub 2006 Aug 8.
• [88] Discovery of antiandrogen activity of nonsteroidal scaffolds of marketed drugs. Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11927-32. doi: 10.1073/pnas.0609752104. Epub 2007 Jul 2.
• [89] Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors. Mol Pharmacol. 1996 Feb;49(2):253-9.
• [90] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [91] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [92] GABA alpha6 receptors mediate midazolam-induced anxiolysis. J Clin Anesth. 2002 May;14(3):206-9. doi: 10.1016/s0952-8180(02)00343-4.
• [93] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.