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Identification
NameIsometheptene
Accession NumberDB06706
TypeSmall Molecule
GroupsApproved
DescriptionIsometheptene is a sympathomimetic drug which causes vasoconstriction. It is used for treating migraines and tension headaches.
Structure
Thumb
Synonyms
Isometheptene
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Isometheptene Mucate, Caffeine, and AcetaminophenXspire Pharma
Isometheptene Mucate, Dichloralphenazone, and AcetaminophenMacoven Pharmaceuticals
Isometheptene Mucate/dichloralphenazone/acetaminophenEci Pharmaceuticals Llc
Isometheptene-dichloral-apap OralAv Kare, Inc.
NodolorMacoven Pharmaceuticals
ProdrinGentex Pharma
Salts
Name/CASStructureProperties
Isometheptene mucate
ThumbNot applicableDBSALT001313
Categories
UNIIY7L24THH6T
CAS number503-01-5
WeightAverage: 141.2539
Monoisotopic: 141.151749613
Chemical FormulaC9H19N
InChI KeyInChIKey=XVQUOJBERHHONY-UHFFFAOYSA-N
InChI
InChI=1S/C9H19N/c1-8(2)6-5-7-9(3)10-4/h6,9-10H,5,7H2,1-4H3
IUPAC Name
methyl(6-methylhept-5-en-2-yl)amine
SMILES
CNC(C)CCC=C(C)C
Taxonomy
ClassificationNot classified
Pharmacology
IndicationIsometheptene is a sympathomimetic drug which causes vasoconstriction. It is used for treating migraines and tension headaches.
PharmacodynamicsIsometheptene Mucate is an indirect-acting sympathomimetic. Due to its vasoconstricting properties, Isometheptene Mucate is used for the treatment of acute migraine attacks, usually in combination with other analgeics. It can also displace catecholamines from vesicles inside the neuron leading to the sympathetic responses it is known for.
Mechanism of actionIsometheptene's vasoconstricting properties arise through activation of the sympathetic nervous system via epinephrine and norepinephrine (or their molecular analogues as is the case with this drug). These compounds elicites smooth muscle activation leading to vasoconstriction. These compounds interact with cell surface adrenergic receptors. Such stimuli result in a signal transduction cascade that leads to increased intracellular calcium from the sarcoplasmic reticulum through IP3 mediated calcium release, as well as enhanced calcium entry across the sarcolemma through calcium channels. The rise in intracellular calcium complexes with calmodulin, which in turn activates myosin light chain kinase. This enzyme is responsible for phosphorylating the light chain of myosin to stimulate cross bridge cycling. Once elevated, the intracellular calcium concentration is returned to its basal level through a variety of protein pumps and calcium exchangers located on the plasma membrane and sarcoplasmic reticulum. This reduction in calcium removes the stimulus necessary for contraction allowing for a return to baseline. The drug can also cause vesicular displacement of noradrenaline from the neuron into the synapse with a similar effect as tyramine.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9876
Blood Brain Barrier+0.9388
Caco-2 permeable+0.6722
P-glycoprotein substrateNon-substrate0.5931
P-glycoprotein inhibitor IInhibitor0.5
P-glycoprotein inhibitor IINon-inhibitor0.7807
Renal organic cation transporterNon-inhibitor0.7631
CYP450 2C9 substrateNon-substrate0.8385
CYP450 2D6 substrateNon-substrate0.5252
CYP450 3A4 substrateSubstrate0.5077
CYP450 1A2 substrateNon-inhibitor0.8046
CYP450 2C9 inhibitorNon-inhibitor0.9172
CYP450 2D6 inhibitorNon-inhibitor0.7719
CYP450 2C19 inhibitorNon-inhibitor0.9108
CYP450 3A4 inhibitorNon-inhibitor0.9752
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8181
Ames testNon AMES toxic0.8476
CarcinogenicityNon-carcinogens0.7545
BiodegradationReady biodegradable0.7933
Rat acute toxicity2.2809 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9048
hERG inhibition (predictor II)Non-inhibitor0.8956
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral
Tabletoral
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility3.06 mg/mLALOGPS
logP2.07ALOGPS
logP2.32ChemAxon
logS-1.7ALOGPS
pKa (Strongest Basic)10.67ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity47.59 m3·mol-1ChemAxon
Polarizability18.81 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

U.S. Patent 2,230,753
U.S. Patent 2,230,754

General ReferencesNot Available
External Links
ATC CodesA03AX10
AHFS Codes
  • 12:12.04
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINEThe risk or severity of adverse effects can be increased when 7,8-DICHLORO-1,2,3,4-TETRAHYDROISOQUINOLINE is combined with Isometheptene.
BenmoxinThe risk or severity of adverse effects can be increased when Benmoxin is combined with Isometheptene.
CaroxazoneThe risk or severity of adverse effects can be increased when Caroxazone is combined with Isometheptene.
DapsoneThe risk or severity of adverse effects can be increased when Dapsone is combined with Isometheptene.
FurazolidoneThe risk or severity of adverse effects can be increased when Furazolidone is combined with Isometheptene.
HydracarbazineThe risk or severity of adverse effects can be increased when Hydracarbazine is combined with Isometheptene.
IproclozideThe risk or severity of adverse effects can be increased when Iproclozide is combined with Isometheptene.
IproniazidThe risk or severity of adverse effects can be increased when Iproniazid is combined with Isometheptene.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Isometheptene.
MebanazineThe risk or severity of adverse effects can be increased when Mebanazine is combined with Isometheptene.
Methylene blueThe risk or severity of adverse effects can be increased when Methylene blue is combined with Isometheptene.
MinaprineThe risk or severity of adverse effects can be increased when Minaprine is combined with Isometheptene.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Isometheptene.
NialamideThe risk or severity of adverse effects can be increased when Nialamide is combined with Isometheptene.
Nitric OxideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Isometheptene.
OctamoxinThe risk or severity of adverse effects can be increased when Octamoxin is combined with Isometheptene.
PargylineThe risk or severity of adverse effects can be increased when Pargyline is combined with Isometheptene.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Isometheptene.
PheniprazineThe risk or severity of adverse effects can be increased when Pheniprazine is combined with Isometheptene.
PhenoxypropazineThe risk or severity of adverse effects can be increased when Phenoxypropazine is combined with Isometheptene.
PirlindoleThe risk or severity of adverse effects can be increased when Pirlindole is combined with Isometheptene.
PivhydrazineThe risk or severity of adverse effects can be increased when Pivhydrazine is combined with Isometheptene.
PrilocaineThe risk or severity of adverse effects can be increased when Isometheptene is combined with Prilocaine.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Isometheptene.
SafrazineThe risk or severity of adverse effects can be increased when Safrazine is combined with Isometheptene.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Isometheptene.
Sodium NitriteThe risk or severity of adverse effects can be increased when Isometheptene is combined with Sodium Nitrite.
ToloxatoneThe risk or severity of adverse effects can be increased when Toloxatone is combined with Isometheptene.
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Trans-2-Phenylcyclopropylamine is combined with Isometheptene.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Isometheptene.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Valdivia LF, Centurion D, Perusquia M, Arulmani U, Saxena PR, Villalon CM: Pharmacological analysis of the mechanisms involved in the tachycardic and vasopressor responses to the antimigraine agent, isometheptene, in pithed rats. Life Sci. 2004 May 14;74(26):3223-34. [PubMed:15094323 ]
  2. Parker EM, Cubeddu LX: Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding. J Pharmacol Exp Ther. 1988 Apr;245(1):199-210. [PubMed:3129549 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis.
Gene Name:
SLC18A2
Uniprot ID:
Q05940
Molecular Weight:
55712.075 Da
References
  1. Valdivia LF, Centurion D, Perusquia M, Arulmani U, Saxena PR, Villalon CM: Pharmacological analysis of the mechanisms involved in the tachycardic and vasopressor responses to the antimigraine agent, isometheptene, in pithed rats. Life Sci. 2004 May 14;74(26):3223-34. [PubMed:15094323 ]
  2. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613 ]
  3. Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A: Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci. 1995 May;15(5 Pt 2):4102-8. [PubMed:7751968 ]
  4. Parker EM, Cubeddu LX: Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding. J Pharmacol Exp Ther. 1988 Apr;245(1):199-210. [PubMed:3129549 ]
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Drug created on May 15, 2010 18:52 / Updated on August 17, 2016 12:24