Identification

Name
Minaprine
Accession Number
DB00805  (APRD00735)
Type
Small Molecule
Groups
Approved
Description

Minaprine is a psychotropic drug which has proved to be effective in the treatment of various depressive states. Like most antidepressants minaprine antagonizes behavioral despair. Minaprine is an amino-phenylpyridazine antidepressant reported to be relatively free of cardiotoxicity, drowsiness, and weight gain.

Structure
Thumb
Synonyms
  • 4-(2-((4-Methyl-6-phenyl-3-pyridazinyl)amino)ethyl)morpholine
  • 4-Methyl-3-(2-morpholinoethylamino)-6-phenylpyridazin
  • Minaprina
  • Minaprinum
  • N-(4-Methyl-6-phenyl-3-pyridazinyl)-4-morpholineethanamine
Product Ingredients
IngredientUNIICASInChI Key
Minaprine Dihydrochloride82Y7NT6DFT25953-17-7GNUCGROXDZMCJI-UHFFFAOYSA-N
International/Other Brands
Cantor (Sanofi-Aventis)
Categories
UNII
00U7GX0NLM
CAS number
25905-77-5
Weight
Average: 298.3828
Monoisotopic: 298.179361346
Chemical Formula
C17H22N4O
InChI Key
LDMWSLGGVTVJPG-UHFFFAOYSA-N
InChI
InChI=1S/C17H22N4O/c1-14-13-16(15-5-3-2-4-6-15)19-20-17(14)18-7-8-21-9-11-22-12-10-21/h2-6,13H,7-12H2,1H3,(H,18,20)
IUPAC Name
4-methyl-N-[2-(morpholin-4-yl)ethyl]-6-phenylpyridazin-3-amine
SMILES
CC1=CC(=NN=C1NCCN1CCOCC1)C1=CC=CC=C1

Pharmacology

Indication

For the treatment of depression

Pharmacodynamics

Minaprine is an amino-phenylpyridazine antidepressant reported to be relatively free of cardiotoxicity, drowsiness, and weight gain. Similar to other antidepressant treatments, minaprine attenuates the beta-adrenergic receptor function. Studies have also shown that minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of minaprine on memory consolidation are related to its dopaminergic action.

Mechanism of action

Minaprine binds to serotonin type 2 receptors and to dopamine D1 and D2 type receptors. It also binds to the serotonin reuptake pump. Therefore, minaprine blocks the reuptake of both dopamine and serotonin. It is also, to a slight degree, cholinomimetic. Thus it may exhibit both mood-brightening and nootropic properties. It also acts as a reversible inhibitor of MAO-A (RIMA).It has also been found to inhibit acetylcholinesterase.

TargetActionsOrganism
AAmine oxidase [flavin-containing] A
inhibitor
Human
A5-hydroxytryptamine receptor 2B
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
A5-hydroxytryptamine receptor 2C
antagonist
Human
AAcetylcholinesterase
inhibitor
Human
USodium-dependent serotonin transporter
inhibitor
Human
UD(1A) dopamine receptor
agonist
Human
UD(2) dopamine receptor
agonist
Human
UMuscarinic acetylcholine receptor M1
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic. Cytochrome P4502D is responsible for the 4-hydroxylation of minaprine to 4-hydroxyminaprine.

Route of elimination
Not Available
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
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Minaprine.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Minaprine.
2,5-Dimethoxy-4-ethylamphetamineMinaprine may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Minaprine.
3,4-MethylenedioxyamphetamineMinaprine may increase the hypertensive activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineMinaprine may increase the hypertensive activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineMinaprine may increase the hypertensive activities of 4-Methoxyamphetamine.
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Minaprine.
5-methoxy-N,N-dimethyltryptamineThe metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Minaprine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineMinaprine may increase the hypertensive activities of 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014943
PubChem Compound
4199
PubChem Substance
46505380
ChemSpider
4054
BindingDB
50074289
ChEBI
51038
ChEMBL
CHEMBL278819
Therapeutic Targets Database
DAP000475
PharmGKB
PA164748351
Wikipedia
Minaprine
ATC Codes
N06AX07 — Minaprine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)122 °CPhysProp
water solubility2360 mg/LNot Available
logP2.03HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0701 mg/mLALOGPS
logP2.15ALOGPS
logP2.19ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)19.25ChemAxon
pKa (Strongest Basic)6.28ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area50.28 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity91.17 m3·mol-1ChemAxon
Polarizability33.82 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+0.9843
Caco-2 permeable+0.5161
P-glycoprotein substrateSubstrate0.7122
P-glycoprotein inhibitor IInhibitor0.5884
P-glycoprotein inhibitor IINon-inhibitor0.6707
Renal organic cation transporterNon-inhibitor0.5938
CYP450 2C9 substrateNon-substrate0.8053
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateNon-substrate0.5794
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.576
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5741
Ames testNon AMES toxic0.7642
CarcinogenicityNon-carcinogens0.7084
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.4667 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7911
hERG inhibition (predictor II)Inhibitor0.6866
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
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 phenylpyridazines. These are organic compounds containing a pyridazine ring substituted by a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyridazines and derivatives
Direct Parent
Phenylpyridazines
Alternative Parents
Morpholines / Imidolactams / Benzene and substituted derivatives / Heteroaromatic compounds / Trialkylamines / Oxacyclic compounds / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenylpyridazine / Monocyclic benzene moiety / Morpholine / Oxazinane / Benzenoid / Imidolactam / Heteroaromatic compound / Tertiary aliphatic amine / Tertiary amine / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
secondary amine, pyridazines, morpholines (CHEBI:51038)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Kan JP, Mouget-Goniot C, Worms P, Biziere K: Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat. Biochem Pharmacol. 1986 Mar 15;35(6):973-8. [PubMed:3954800]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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]
  3. Kodama K, Shibata S, Ueki S: Protective effect of minaprine against the abnormal changes of 2-deoxyglucose uptake by rat hippocampal slices induced by hypoxia/hypoglycemia. Jpn J Pharmacol. 1992 Sep;60(1):33-8. [PubMed:1361012]
  4. Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Chaki S, Aihara H: 5-HT2 antagonists and minaprine block the 5-HT-induced inhibition of dopamine release from rat brain striatal slices. Eur J Pharmacol. 1988 Aug 9;153(1):89-95. [PubMed:2975224]
  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
Yes
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. Kodama K, Shibata S, Ueki S: Protective effect of minaprine against the abnormal changes of 2-deoxyglucose uptake by rat hippocampal slices induced by hypoxia/hypoglycemia. Jpn J Pharmacol. 1992 Sep;60(1):33-8. [PubMed:1361012]
  2. Nabeshima T, Kawashima K, Kameyama T: Effect of minaprine on cycloheximide-induced amnesia in mice. Eur J Pharmacol. 1989 Oct 10;169(2-3):249-57. [PubMed:2530096]
  3. Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Chaki S, Aihara H: 5-HT2 antagonists and minaprine block the 5-HT-induced inhibition of dopamine release from rat brain striatal slices. Eur J Pharmacol. 1988 Aug 9;153(1):89-95. [PubMed:2975224]
  4. Biziere K, Worms P, Kan JP, Mandel P, Garattini S, Roncucci R: Minaprine, a new drug with antidepressant properties. Drugs Exp Clin Res. 1985;11(12):831-40. [PubMed:3836113]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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]
  3. Kodama K, Shibata S, Ueki S: Protective effect of minaprine against the abnormal changes of 2-deoxyglucose uptake by rat hippocampal slices induced by hypoxia/hypoglycemia. Jpn J Pharmacol. 1992 Sep;60(1):33-8. [PubMed:1361012]
  4. Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Chaki S, Aihara H: 5-HT2 antagonists and minaprine block the 5-HT-induced inhibition of dopamine release from rat brain striatal slices. Eur J Pharmacol. 1988 Aug 9;153(1):89-95. [PubMed:2975224]
Details
5. Acetylcholinesterase
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Duarte CD, Barreiro EJ, Fraga CA: Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19. [PubMed:18045214]
  2. Contreras JM, Rival YM, Chayer S, Bourguignon JJ, Wermuth CG: Aminopyridazines as acetylcholinesterase inhibitors. J Med Chem. 1999 Feb 25;42(4):730-41. [PubMed:10052979]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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. Duarte CD, Barreiro EJ, Fraga CA: Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19. [PubMed:18045214]
  2. Worms P, Kan JP, Steinberg R, Terranova JP, Perio A, Biziere K: Cholinomimetic activities of minaprine. Naunyn Schmiedebergs Arch Pharmacol. 1989 Oct;340(4):411-8. [PubMed:2586634]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:40