Identification

Name
Molindone
Accession Number
DB01618
Type
Small Molecule
Groups
Approved
Description

An indole derivative effective in schizophrenia and other psychoses and possibly useful in the treatment of the aggressive type of undersocialized conduct disorder. Molindone has much lower affinity for D2 receptors than most antipsychotic agents and has a relatively low affinity for D1 receptors. It has only low to moderate affinity for cholinergic and alpha-adrenergic receptors. Some electrophysiologic data from animals indicate that molindone has certain characteristics that resemble those of clozapine. (From AMA Drug Evaluations Annual, 1994, p283)

Structure
Thumb
Synonyms
  • (+-)-molindone
  • Molindona
  • Molindone
  • Molindonum
Product Ingredients
IngredientUNIICASInChI Key
Molindone hydrochloride1DWS68PNE615622-65-8GQWNECFJGBQMBO-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MobanTablet50 mg/1OralEndo Pharmaceuticals1974-07-03Not applicableUs
MobanTablet5 mg/1OralEndo Pharmaceuticals1974-07-03Not applicableUs
MobanTablet25 mg/1OralEndo Pharmaceuticals1974-07-03Not applicableUs
MobanTablet50 mg/1OralPhysicians Total Care, Inc.1974-07-032011-06-30Us
MobanTablet10 mg/1OralEndo Pharmaceuticals1974-07-03Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Molindone HydrochlorideTablet5 mg/1OralCore Pharma, Llc2015-09-152017-07-31Us
Molindone HydrochlorideTablet25 mg/1OralCore Pharma, Llc2015-09-152018-03-31Us
Molindone HydrochlorideTablet10 mg/1OralCore Pharma, Llc2015-09-152018-02-28Us
International/Other Brands
Moban
Categories
UNII
RT3Y3QMF8N
CAS number
7416-34-4
Weight
Average: 276.374
Monoisotopic: 276.183778022
Chemical Formula
C16H24N2O2
InChI Key
KLPWJLBORRMFGK-UHFFFAOYSA-N
InChI
InChI=1S/C16H24N2O2/c1-3-13-11(2)17-14-5-4-12(16(19)15(13)14)10-18-6-8-20-9-7-18/h12,17H,3-10H2,1-2H3
IUPAC Name
3-ethyl-2-methyl-5-(morpholin-4-ylmethyl)-4,5,6,7-tetrahydro-1H-indol-4-one
SMILES
CCC1=C(C)NC2=C1C(=O)C(CN1CCOCC1)CC2

Pharmacology

Indication

Molindone is used for the management of the manifestations of psychotic disorders.

Associated Conditions
Pharmacodynamics

Molindone is a dihydroindolone compound which is not structurally related to the phenothiazines, the butyrophenones, or the thioxanthenes. Molindone has a pharmacological profile in laboratory animals which predominantly resembles that of major tranquilizers causing reduction of spontaneous locomotion and aggressiveness, suppression of a conditioned response and antagonism of the bizarre stereotyped behavior and hyperactivity induced by amphetamines. In addition, molindone antagonizes the depression caused by the tranquilizing agent tetrabenazine.

Mechanism of action

The exact mechanism has not been established, however, based on electroencephalogram (EEG) studies, molindone is thought to act by occupying (antagonizing) dopamine (D2) receptor sites in the reticular limbic systems in the brain, thus decreasing dopamine activity. Decreased dopamine activity results in decreased physiological effects normally induced by excessive dopamine stimulation, such as those typically seen in manifestations of psychotic disorders.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
U5-hydroxytryptamine receptor 1A
antagonist
Human
U5-hydroxytryptamine receptor 2A
antagonist
Human
UMuscarinic acetylcholine receptor M1
other/unknown
Human
Absorption

Rapidly absorbed from the gastrointestinal tract following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Most likely hepatic. 36 metabolites have been recognized, some of which may be active.

Route of elimination

Human metabolic studies show molindone to be rapidly absorbed and metabolized when given orally. There are 36 recognized metabolites with less than 2-3% unmetabolized molindone being excreted in urine and feces.

Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineMolindone may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineMolindone may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineMolindone may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineMolindone may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Molindone is combined with 7-Nitroindazole.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Molindone.
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Molindone.
AcetazolamideThe risk or severity of adverse effects can be increased when Molindone is combined with Acetazolamide.
AdipiplonThe risk or severity of adverse effects can be increased when Molindone is combined with Adipiplon.
AgomelatineThe risk or severity of adverse effects can be increased when Molindone is combined with Agomelatine.
Food Interactions
Not Available

References

Synthesis Reference
US3491093
General References
Not Available
External Links
Human Metabolome Database
HMDB0015555
KEGG Compound
C07230
PubChem Compound
23897
PubChem Substance
46504744
ChemSpider
22342
BindingDB
50130290
ChEBI
6965
ChEMBL
CHEMBL460
Therapeutic Targets Database
DAP000979
PharmGKB
PA164746756
IUPHAR
207
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Molindone
ATC Codes
N05AE02 — Molindone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentImpulsive Aggression Comorbid With ADHD in Children1
4CompletedTreatmentSchizophrenic Disorders1
Not AvailableRecruitingNot AvailableAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiolysis / Arterial Hypotension / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infections / Convulsions / Cyanide Poisoning / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Early-onset Schizophrenia Spectrum Disorders / Edema / Epilepsies / Feeling Anxious / Flu caused by Influenza / Gastroparesis / Gynaecological infection / Headaches / Herpes Simplex Virus / High Blood Pressure (Hypertension) / High Cholesterol / Hospital-acquired bacterial pneumonia / Hyperlipidemias / Infantile Hemangiomas / Infection NOS / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Migraines / Muscle Spasms / Nausea / Opioid Addiction / Pain / Plague / Pneumonia / Prophylaxis / Psittacosis / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenic Disorders / Sedation therapy / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections / Stable Angina (SA) / Thromboprophylaxis / Thrombosis / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infections (UTIs) / Vomiting / Withdrawal1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bristol-Myers Squibb Co.
  • Endo Pharmaceuticals Inc.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
TabletOral10 mg/1
TabletOral25 mg/1
TabletOral5 mg/1
TabletOral50 mg/1
Prices
Unit descriptionCostUnit
Moban 50 mg tablet5.12USD tablet
Moban 25 mg tablet3.02USD tablet
Moban 10 mg tablet2.57USD tablet
Moban 5 mg tablet1.79USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.474 mg/mLALOGPS
logP2.09ALOGPS
logP2.04ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)15.34ChemAxon
pKa (Strongest Basic)6.65ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area45.33 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity81.06 m3·mol-1ChemAxon
Polarizability32 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9637
Caco-2 permeable+0.6401
P-glycoprotein substrateSubstrate0.7994
P-glycoprotein inhibitor IInhibitor0.828
P-glycoprotein inhibitor IIInhibitor0.6826
Renal organic cation transporterInhibitor0.5863
CYP450 2C9 substrateNon-substrate0.8202
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.637
CYP450 1A2 substrateNon-inhibitor0.6779
CYP450 2C9 inhibitorNon-inhibitor0.939
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.7549
CYP450 3A4 inhibitorInhibitor0.7739
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7134
Ames testNon AMES toxic0.6399
CarcinogenicityNon-carcinogens0.9336
BiodegradationNot ready biodegradable0.9909
Rat acute toxicity2.9352 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5259
hERG inhibition (predictor II)Inhibitor0.5804
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.41 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indoles and derivatives. These are organic compounds containing an indole, which is a bicyclic ring system made up of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Not Available
Direct Parent
Indoles and derivatives
Alternative Parents
Aryl alkyl ketones / Aralkylamines / Substituted pyrroles / Morpholines / Vinylogous amides / Heteroaromatic compounds / Trialkylamines / Oxacyclic compounds / Dialkyl ethers / Azacyclic compounds
show 3 more
Substituents
Indole or derivatives / Aryl ketone / Aryl alkyl ketone / Aralkylamine / Morpholine / Oxazinane / Substituted pyrrole / Pyrrole / Heteroaromatic compound / Vinylogous amide
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
indoles (CHEBI:6965)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  2. Seeman P, Tallerico T: Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors. Mol Psychiatry. 1998 Mar;3(2):123-34. [PubMed:9577836]
  3. Lidow MS, Goldman-Rakic PS: Differential regulation of D2 and D4 dopamine receptor mRNAs in the primate cerebral cortex vs. neostriatum: effects of chronic treatment with typical and atypical antipsychotic drugs. J Pharmacol Exp Ther. 1997 Nov;283(2):939-46. [PubMed:9353417]
  4. Froimowitz M, Cody V: The incorporation of butyrophenones and related compounds into a pharmacophore for dopamine D2 antagonists. Drug Des Discov. 1997 Aug;15(2):63-81. [PubMed:9342550]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Nguyen TV, Juorio AV: Down-regulation of tryptamine binding sites following chronic molindone administration. A comparison with responses of dopamine and 5-hydroxytryptamine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1989 Oct;340(4):366-71. [PubMed:2586632]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Nguyen TV, Juorio AV: Down-regulation of tryptamine binding sites following chronic molindone administration. A comparison with responses of dopamine and 5-hydroxytryptamine receptors. Naunyn Schmiedebergs Arch Pharmacol. 1989 Oct;340(4):366-71. [PubMed:2586632]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. Neeper R, Richelson E, Nelson A: Neuroleptic binding to muscarinic M2 receptors of normal human heart in vitro and comparison with binding to M1 and dopamine D2 receptors of brain. Neuropharmacology. 1991 May;30(5):527-9. [PubMed:1678146]

Drug created on August 29, 2007 14:15 / Updated on October 01, 2018 16:35