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Identification
NameIsometheptene
Accession NumberDB06706
TypeSmall Molecule
GroupsApproved
Description

Isometheptene 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
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Isometheptene.
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Isometheptene.
BenzphetamineThe risk or severity of adverse effects can be increased when Benzphetamine is combined with Isometheptene.
BortezomibThe metabolism of Isometheptene can be decreased when combined with Bortezomib.
ButabarbitalThe metabolism of Isometheptene can be increased when combined with Butabarbital.
ButethalThe metabolism of Isometheptene can be increased when combined with Butethal.
ChlorphentermineThe risk or severity of adverse effects can be increased when Chlorphentermine is combined with Isometheptene.
ClenbuterolThe risk or severity of adverse effects can be increased when Clenbuterol is combined with Isometheptene.
DapsoneThe risk or severity of adverse effects can be increased when Dapsone is combined with Isometheptene.
DicoumarolIsometheptene may increase the anticoagulant activities of Dicoumarol.
DobutamineThe risk or severity of adverse effects can be increased when Dobutamine is combined with Isometheptene.
DopamineThe risk or severity of adverse effects can be increased when Dopamine is combined with Isometheptene.
DoxofyllineThe risk or severity of adverse effects can be increased when Isometheptene is combined with Doxofylline.
DronabinolDronabinol may increase the tachycardic activities of Isometheptene.
EpinephrineThe risk or severity of adverse effects can be increased when Epinephrine is combined with Isometheptene.
EthanolEthanol may increase the hepatotoxic activities of Isometheptene.
FenoterolThe risk or severity of adverse effects can be increased when Fenoterol is combined with Isometheptene.
FluvoxamineThe metabolism of Isometheptene can be decreased when combined with Fluvoxamine.
FormoterolThe risk or severity of adverse effects can be increased when Formoterol is combined with Isometheptene.
HeptabarbitalThe metabolism of Isometheptene can be increased when combined with Heptabarbital.
HexobarbitalThe metabolism of Isometheptene can be increased when combined with Hexobarbital.
IobenguaneThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Isometheptene.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Isometheptene.
IsoprenalineThe risk or severity of adverse effects can be increased when Isoprenaline is combined with Isometheptene.
LabetalolThe risk or severity of adverse effects can be increased when Labetalol is combined with Isometheptene.
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Isometheptene.
MephentermineThe risk or severity of adverse effects can be increased when Mephentermine is combined with Isometheptene.
MetaraminolThe risk or severity of adverse effects can be increased when Metaraminol is combined with Isometheptene.
MethamphetamineThe risk or severity of adverse effects can be increased when Methamphetamine is combined with Isometheptene.
MethohexitalThe metabolism of Isometheptene can be increased when combined with Methohexital.
MethoxamineThe risk or severity of adverse effects can be increased when Methoxamine is combined with Isometheptene.
MexiletineThe metabolism of Isometheptene can be decreased when combined with Mexiletine.
MidodrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Isometheptene.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Isometheptene.
NaphazolineThe risk or severity of adverse effects can be increased when Naphazoline is combined with Isometheptene.
NorepinephrineThe risk or severity of adverse effects can be increased when Norepinephrine is combined with Isometheptene.
OrciprenalineThe risk or severity of adverse effects can be increased when Orciprenaline is combined with Isometheptene.
OxymetazolineThe risk or severity of adverse effects can be increased when Oxymetazoline is combined with Isometheptene.
PentobarbitalThe metabolism of Isometheptene can be increased when combined with Pentobarbital.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Isometheptene.
PhenmetrazineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Isometheptene.
PhentermineThe risk or severity of adverse effects can be increased when Phentermine is combined with Isometheptene.
PhenylephrineThe serum concentration of Phenylephrine can be increased when it is combined with Isometheptene.
PhenylpropanolamineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with Isometheptene.
PhenytoinThe serum concentration of Isometheptene can be decreased when it is combined with Phenytoin.
PrimidoneThe metabolism of Isometheptene can be increased when combined with Primidone.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Isometheptene.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Isometheptene.
RitodrineThe risk or severity of adverse effects can be increased when Ritodrine is combined with Isometheptene.
SalmeterolThe risk or severity of adverse effects can be increased when Salmeterol is combined with Isometheptene.
SecobarbitalThe metabolism of Isometheptene can be increased when combined with Secobarbital.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Isometheptene.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Isometheptene.
TerbutalineThe risk or severity of adverse effects can be increased when Terbutaline 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