Loperamide

Summary

Loperamide (CHEMBL841) is an approved small-molecule μ-opioid receptor agonist (ATC A07DA03) targeting OPRM1; indicated across 12 conditions including non-small cell lung carcinoma and diarrheal disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A07DA03 (+1 more)
• Targets: 1 (OPRM1)
• Indications: 12 conditions
• Clinical trials: 54
• Chemistry: 477 Da · C29H33ClN2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL841
Name	Loperamide
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3955
ChEBI	CHEBI:6532
ATC	A07DA03, A07DA53
Molecular formula	C29H33ClN2O2
Molecular weight	477
InChIKey	RDOIQAHITMMDAJ-UHFFFAOYSA-N

SMILES: CN(C)C(=O)C(CCN1CCC(CC1)(C2=CC=C(C=C2)Cl)O)(C3=CC=CC=C3)C4=CC=CC=C4

IUPAC name: 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide

ChEBI definition: A synthetic piperidine derivative, effective against diarrhoea resulting from gastroenteritis or inflammatory bowel disease.

Pharmacological roles (ChEBI): μ-opioid receptor agonist, antidiarrhoeal drug, anticoronaviral agent.

Also known as: Loperamida, Loperamide, loperamide, SID11111380, SID11112740, SID11113732, SID26751916, SID26751917, SID90340730, SID104171181, SID50104594, SID50104595

Parent form; salt/anhydrous children: CHEMBL1707

Patent coverage: 6,208 distinct patent families (22,587 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
OPRM1	μ receptor	Agonist	9.28	0%	P35372

Broader ChEMBL bioactivity targets: 56 (assay-derived). Sample: Ubiquitin carboxyl-terminal hydrolase 2, Nuclear receptor ROR-gamma, Survival motor neuron protein, Prelamin-A/C, Inositol monophosphatase 1, Thrombopoietin, Ras-related protein Rab-9A, Menin, Somatostatin receptor type 5, 5-hydroxytryptamine receptor 2B.

Bioactivity

ChEMBL activities: 59 potent at pChembl ≥ 5 of 98 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P33535	9.8	Ki	0.16	nM	CHEMBL_ACT_1469591
OPRM1	9.57	Ki	0.27	nM	CHEMBL_ACT_24411910
OPRM1	9.28	Ki	0.53	nM	CHEMBL_ACT_1455200
OPRM1	9.23	Ki	0.59	nM	CHEMBL_ACT_7774538
OPRM1	8.84	IC50	1.45	nM	CHEMBL_ACT_7774537
OPRM1	8.52	AC50	3	nM	CHEMBL_ACT_25158116
CYP2D6	7.8	Potency	15.8	nM	CHEMBL_ACT_5006548
CYP2D6	7.8	AC50	15.85	nM	CHEMBL_ACT_5986804
KCNH2	7.48	IC50	33	nM	CHEMBL_ACT_18479625
P33533	7.3	Ki	50.1	nM	CHEMBL_ACT_1469590
P97266	7.24	EC50	58	nM	CHEMBL_ACT_1469594
OPRD1	6.81	EC50	156	nM	CHEMBL_ACT_1469593
SCN5A	6.62	IC50	239	nM	CHEMBL_ACT_18479626
SIGMAR1	6.58	Ki	264	nM	CHEMBL_ACT_7774610
SCN1A	6.57	IC50	270	nM	CHEMBL_ACT_352496
OPRD1	6.5	Ki	316	nM	CHEMBL_ACT_7774534
DRD3	6.34	Ki	454	nM	CHEMBL_ACT_7772479
P15823	6.27	Ki	534	nM	CHEMBL_ACT_7772403
SIGMAR1	6.2	IC50	628	nM	CHEMBL_ACT_7774609
KCNH2	6.16	AC50	689.4	nM	CHEMBL_ACT_25117521
OPRD1	6.05	IC50	896	nM	CHEMBL_ACT_7774533
P15823	6.01	IC50	965	nM	CHEMBL_ACT_7772402
SLC6A4	5.93	Ki	1170	nM	CHEMBL_ACT_7774608
TSHR	5.9	Potency	1259	nM	CHEMBL_ACT_3934341
TSHR	5.9	Potency	1259	nM	CHEMBL_ACT_4691431
OPRK1	5.9	Ki	1250	nM	CHEMBL_ACT_7774536
DRD3	5.87	IC50	1337	nM	CHEMBL_ACT_7772478
CES2	5.82	Ki	1500	nM	CHEMBL_ACT_22800782
DRD4	5.73	Ki	1850	nM	CHEMBL_ACT_24412003
DRD3	5.71	Ki	1940	nM	CHEMBL_ACT_24411957

Target pathways

Aggregated over 1 target gene(s): OPRM1.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Opioid Signalling	1	OPRM1
G-protein activation	1	OPRM1
Peptide ligand-binding receptors	1	OPRM1
G alpha (i) signalling events	1	OPRM1
Interleukin-4 and Interleukin-13 signaling	1	OPRM1
MECP2 regulates neuronal receptors and channels	1	OPRM1

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	1
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
neuropeptide signaling pathway	1
sensory perception	1
negative regulation of cell population proliferation	1
sensory perception of pain	1
G protein-coupled opioid receptor signaling pathway	1
negative regulation of nitric oxide biosynthetic process	1
behavioral response to ethanol	1
positive regulation of neurogenesis	1
negative regulation of cytosolic calcium ion concentration	1
negative regulation of Wnt protein secretion	1

Indications & clinical

Indications

12 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
diarrheal disease	3	MONDO:0001673	HP:0002014
breast carcinoma	2	MONDO:0004989	EFO:0000305
reproductive system disorder	2	MONDO:0005039	EFO:0000512
breast neoplasm	2	MONDO:0021100	EFO:0003869
Clostridium infectious disease	2	MONDO:0024388	EFO:0009130
neoplasm	2	MONDO:0005070	MONDO:0004992
intestinal obstruction	1	MONDO:0004565	MONDO:0004565

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 54.

Phase distribution

Phase	Trials
PHASE2	14
PHASE1	13
PHASE3	7
Not specified	7
PHASE4	5
PHASE2/PHASE3	5
PHASE1/PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05677282	PHASE4	RECRUITING	Single Dose Antibiotic Treatment of Acute Watery Diarrhea, Rifaximin Versus Azithromycin, With Loperamide Adjunct
NCT00292344	PHASE4	COMPLETED	Rifaximin, Loperamide and the Combination to Treat Travelers’ Diarrhea
NCT00359970	PHASE4	COMPLETED	Azithromycin, With or Without Loperamide, to Treat Travelers’ Diarrhea
NCT00591357	PHASE4	SUSPENDED	Efficacy of Loperamide for C. Difficile Colitis and Other Diarrheal Diseases Associated With Antibiotic Therapy
NCT02217982	PHASE4	TERMINATED	Pilot Study to Assess Dimethyl Fumarate Related GI Symptom Mitigation
NCT00003057	PHASE3	COMPLETED	Octreotide Compared With Loperamide Hydrochloride for Chemotherapy-Related Diarrhea in Patients With Colorectal Cancer
NCT00650637	PHASE3	TERMINATED	A Study to Determine Effective Prophylaxis and Treatment of Nelfinavir-Associated Diarrhea
NCT00727649	PHASE2/PHASE3	COMPLETED	Efficacy and Mechanisms of Pharmacologic Treatment of Fecal Incontinence
NCT01350570	PHASE2/PHASE3	COMPLETED	Acupuncture for Patients With Diarrhea-predominant IBS or Functional Diarrhea: a Randomized Controlled Trial
NCT01814553	PHASE3	COMPLETED	ADAM-Afatinib Diarrhea Assessment and Management
NCT02008565	PHASE3	COMPLETED	Controlling Anal Incontinence by Performing Anal Exercises With Biofeedback or Loperamide (CAPABLe)
NCT02099006	PHASE2/PHASE3	COMPLETED	Novel Topical Therapies for the Treatment of Genital Pain
NCT02263365	PHASE3	TERMINATED	Use of Post Operative Loperamide in Colorectal Patients After Diverting Ileostomies
NCT02266849	PHASE3	TERMINATED	Loperamide vs. Placebo’s Effect on Ileostomy Output: A Clinical Randomized Blinded Cross-over Study
NCT02340481	PHASE3	COMPLETED	Efficacy and Safety Study of Loperamide Hydrochloride/Simethicone Chewable Tablet in Treatment of Acute Diarrhea With Abdominal Discomfort and Flatulence
NCT02686645	PHASE2/PHASE3	UNKNOWN	Fecal Microbiota Therapy for Recurrent Clostridium Difficile Infection
NCT04736186	PHASE2/PHASE3	UNKNOWN	Prevention and Treatment of Pyrrolitinib-associated Diarrhea
NCT02747004	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer
NCT05252988	PHASE2	ACTIVE_NOT_RECRUITING	Three Antidiarrheal Strategies in HER2+/HR+ Early Breast Cancer Patients Treated With Extended Adjuvant Neratinib
NCT07426822	PHASE2	NOT_YET_RECRUITING	Rash & Diarrhea Prophylaxis With Capivasertib
NCT00401388	PHASE2	COMPLETED	A Trial of Perifosine in Patients With Chemo-Insensitive Sarcomas
NCT01391962	PHASE2	COMPLETED	Sunitinib or Cediranib for Alveolar Soft Part Sarcoma
NCT02323516	PHASE2	WITHDRAWN	Evaluation of the Efficacy of Low-dose Acetylsalicylic Acid on Diarrhea Induced by Anti-cancer Targeted Therapies.
NCT02400476	PHASE2	COMPLETED	An Open-Label Study to Characterize the Incidence and Severity of Diarrhea in Patients With Early-Stage HER2+ Breast Cancer Treated With Neratinib and Loperamide
NCT02441946	PHASE2	COMPLETED	A Neoadjuvant Study of Abemaciclib (LY2835219) in Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Breast Cancer
NCT02858310	PHASE1/PHASE2	COMPLETED	E7 TCR T Cells for Human Papillomavirus-Associated Cancers
NCT03094052	PHASE2	COMPLETED	Incidence and Severity of Diarrhea in Patients With HER2 Positive Breast Cancer Treated With Trastuzumab and Neratinib
NCT03705442	PHASE2	UNKNOWN	Probiotics as Adjuvant Therapy in the Treatment of Metastatic Colorectal Cancer
NCT04172597	PHASE2	TERMINATED	A Study of Poziotinib in Patients With Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Activating Mutations in Advanced Malignancies
NCT04366713	PHASE2	COMPLETED	A Study to Characterize Colon Pathology in Patients With HER2 Amplified Breast Cancer Treated With Neratinib
NCT04823065	PHASE1/PHASE2	COMPLETED	4FMFES-PET Imaging of Endometrial and Ovarian Cancers
NCT05520723	PHASE2	COMPLETED	Preventive stRategy for IMMU132-relatED AEs in TNBC or Luminal Breast Cancer- PRIMED
NCT06865677	PHASE2	TERMINATED	Sacituzumab Govitecan for Relapsed Ovarian, Endometrial, and Cervical Carcinomas
NCT02057133	PHASE1	ACTIVE_NOT_RECRUITING	A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread
NCT04038619	PHASE1	RECRUITING	Fecal Microbiota Transplantation in Treating Immune-Checkpoint Inhibitor Induced-Diarrhea or Colitis in Genitourinary Cancer Patients
NCT05528848	PHASE1	ACTIVE_NOT_RECRUITING	Multi-System Analysis of Opioid Receptor Binding
NCT00806299	PHASE1	COMPLETED	Loperamide Grapefruit Juice Interaction PK Trial
NCT00954304	PHASE1	COMPLETED	Duration of P-glycoprotein Inhibition After Oral Administration of HM30181AK Tablet
NCT01596764	PHASE1	COMPLETED	Effects of Methylnaltrexone in Comparison to Naloxone on Loperamide-induced Delay of the Oro-cecal, Whole-gut and Colon Transit Time.
NCT01596777	PHASE1	COMPLETED	Effects of 500 mg Immediate Release and Extended Release Methylnaltrexone on Loperamide-induced Delay of the Oro-cecal and Whole-gut Transit Time in Healthy Subjects

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 4 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

400 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
ELUXADOLINE	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
MAVORIXAFOR	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
ALFENTANIL	ChEMBL	Phase 4 (approved)	OPRM1
ALOGLIPTIN	ChEMBL	Phase 4 (approved)	OPRM1
ALPIDEM	ChEMBL	Phase 4 (approved)	OPRM1
ALVIMOPAN	ChEMBL	Phase 4 (approved)	OPRM1
AMBENONIUM	ChEMBL	Phase 4 (approved)	OPRM1
AMILORIDE	ChEMBL	Phase 4 (approved)	OPRM1
AMIODARONE	ChEMBL	Phase 4 (approved)	OPRM1
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	OPRM1
AMLODIPINE	ChEMBL	Phase 4 (approved)	OPRM1
AMODIAQUINE	ChEMBL	Phase 4 (approved)	OPRM1
AMOXAPINE	ChEMBL	Phase 4 (approved)	OPRM1
ANTAZOLINE	ChEMBL	Phase 4 (approved)	OPRM1
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	OPRM1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	OPRM1
ATOMOXETINE	ChEMBL	Phase 4 (approved)	OPRM1
AZELASTINE	ChEMBL	Phase 4 (approved)	OPRM1
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	OPRM1
BENFLUOREX	ChEMBL	Phase 4 (approved)	OPRM1
BENZBROMARONE	ChEMBL	Phase 4 (approved)	OPRM1
BENZIODARONE	ChEMBL	Phase 4 (approved)	OPRM1
BENZTROPINE	ChEMBL	Phase 4 (approved)	OPRM1
BENZYDAMINE	ChEMBL	Phase 4 (approved)	OPRM1
BEPRIDIL	ChEMBL	Phase 4 (approved)	OPRM1
BEXAROTENE	ChEMBL	Phase 4 (approved)	OPRM1
BITHIONOL	ChEMBL	Phase 4 (approved)	OPRM1
BOSUTINIB	ChEMBL	Phase 4 (approved)	OPRM1
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	OPRM1
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	OPRM1
BROMPERIDOL	ChEMBL	Phase 4 (approved)	OPRM1
BUPRENORPHINE	ChEMBL	Phase 4 (approved)	OPRM1
BUTORPHANOL	ChEMBL	Phase 4 (approved)	OPRM1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	OPRM1
CANNABIDIOL	ChEMBL	Phase 4 (approved)	OPRM1
CARVEDILOL	ChEMBL	Phase 4 (approved)	OPRM1
CASPOFUNGIN	ChEMBL	Phase 4 (approved)	OPRM1
CETRORELIX	ChEMBL	Phase 4 (approved)	OPRM1
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	OPRM1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	OPRM1
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	OPRM1
CINACALCET	ChEMBL	Phase 4 (approved)	OPRM1
CINNARIZINE	ChEMBL	Phase 4 (approved)	OPRM1
CITALOPRAM	ChEMBL	Phase 4 (approved)	OPRM1
CLEMASTINE	ChEMBL	Phase 4 (approved)	OPRM1
CLOMIPHENE	ChEMBL	Phase 4 (approved)	OPRM1
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	OPRM1
CLOPIDOGREL	ChEMBL	Phase 4 (approved)	OPRM1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	OPRM1
COBIMETINIB	ChEMBL	Phase 4 (approved)	OPRM1
CODEINE	ChEMBL	Phase 4 (approved)	OPRM1
CYCLIZINE	ChEMBL	Phase 4 (approved)	OPRM1
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	OPRM1
DANAZOL	ChEMBL	Phase 4 (approved)	OPRM1