DT-Web

DB06706 - Isometheptene


Identification
Name Isometheptene
Accession Number DB06706
Type small molecule
Description Isometheptene is a sympathomimetic drug which causes vasoconstriction. It is used for treating migraines and tension headaches.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 141.2539
Groups approved
Monoisotopic Weight 141.151749613
Pharmacology
Indication Isometheptene is a sympathomimetic drug which causes vasoconstriction. It is used for treating migraines and tension headaches.
Mechanism of action Isometheptene'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.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Not Available
Affected organisms Not Available
Interactions
Drug Interactions
Drug Mechanism of interaction
Desvenlafaxine Desvenlafaxine may increase the tachycardic and vasopressor effects of isometheptene. Consider alternate therapy or monitor for increased sympathomimetic effects, such as increased blood pressure, chest pain and headache.
Food Interactions Not Available

Targets


Alpha-1A adrenergic receptor
Name Alpha-1A adrenergic receptor
Gene Name ADRA1A
Pharmacological action yes
Actions agonist
References
  • 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
  • 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
DTHybrid score 0.3288
Synaptic vesicular amine transporter
Name Synaptic vesicular amine transporter
Gene Name SLC18A2
Pharmacological action yes
Actions inhibitor
References
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.5438

Predictions


Id Partner name Gene Name Score
1636 Trace amine-associated receptor 1 TAAR1 0.1064
318 Alpha-2A adrenergic receptor ADRA2A 0.1059
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0883
632 Alpha-1B adrenergic receptor ADRA1B 0.0867
713 Sodium-dependent dopamine transporter SLC6A3 0.086
4119 Cytochrome P450 2D6 CYP2D6 0.0702
824 Sodium-dependent serotonin transporter SLC6A4 0.0536
502 5-hydroxytryptamine 2A receptor HTR2A 0.0505
831 D(2) dopamine receptor DRD2 0.05
789 Alpha-1D adrenergic receptor ADRA1D 0.0463
3941 Amine oxidase [flavin-containing] A MAOA 0.0412
4512 Cytochrome P450 3A4 CYP3A4 0.0344
3939 Amine oxidase [flavin-containing] B MAOB 0.033
629 Alpha-2B adrenergic receptor ADRA2B 0.0311
1588 Multidrug resistance protein 1 ABCB1 0.03
23 D(1A) dopamine receptor DRD1 0.0291
378 Alpha-2C adrenergic receptor ADRA2C 0.0289
766 Beta-2 adrenergic receptor ADRB2 0.0273
193 Beta-1 adrenergic receptor ADRB1 0.0256
492 Histamine H1 receptor HRH1 0.0245
590 5-hydroxytryptamine 2C receptor HTR2C 0.0243
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0238
320 5-hydroxytryptamine 1A receptor HTR1A 0.0208
982 Cocaine- and amphetamine-regulated transcript protein CARTPT 0.0204
3923 Cholinesterase BCHE 0.0197
6147 Solute carrier family 22 member 3 SLC22A3 0.0195
6145 Solute carrier family 22 member 1 SLC22A1 0.0182
4200 Cytochrome P450 1A2 CYP1A2 0.0178
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0164
474 Acetylcholinesterase ACHE 0.0163
4120 NADPH--cytochrome P450 reductase POR 0.0152
118 Organic cation/carnitine transporter 2 SLC22A5 0.015
6030 Cytochrome P450 2B6 CYP2B6 0.0145
436 5-hydroxytryptamine 2B receptor HTR2B 0.0145
6144 Solute carrier family 22 member 2 SLC22A2 0.0143
4118 Cytochrome P450 3A5 CYP3A5 0.0134
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0133
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0124
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0121
432 D(4) dopamine receptor DRD4 0.0117
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0111
1517 Beta-3 adrenergic receptor ADRB3 0.0111
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0108
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0105
776 Bile salt export pump ABCB11 0.0105
6016 Cytochrome P450 2C19 CYP2C19 0.0093
638 D(3) dopamine receptor DRD3 0.0091
716 5-hydroxytryptamine 7 receptor HTR7 0.0083
5718 Cytochrome P450 2A6 CYP2A6 0.0082
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0082
163 D(1B) dopamine receptor DRD5 0.0081
725 5-hydroxytryptamine 1D receptor HTR1D 0.008
1256 5-hydroxytryptamine 6 receptor HTR6 0.008
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0078
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0078
6013 Cytochrome P450 2E1 CYP2E1 0.0077
4757 Cytochrome P450 2C9 CYP2C9 0.0067
885 5-hydroxytryptamine 1B receptor HTR1B 0.0066
587 Serum albumin ALB 0.0059
465 Calmodulin CALM1 0.0058
6107 Cytochrome P450 3A7 CYP3A7 0.005
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0049
828 Phenylalanine-4-hydroxylase PAH 0.0046
3109 Phenylalanine-4-hydroxylase phhA 0.0046
6138 Multidrug resistance protein 3 ABCB4 0.0043
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0038
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0038
3426 Glutamine synthetase glnA 0.0037
3987 Glutamine synthetase GLUL 0.0037
124 Histamine H2 receptor HRH2 0.0037
528 5-hydroxytryptamine 1E receptor HTR1E 0.0037
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0036
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0035
6859 Protein S100-A4 S100A4 0.0035
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0034
341 5-hydroxytryptamine 3 receptor HTR3A 0.0029
3947 Xanthine dehydrogenase/oxidase XDH 0.0028
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0024
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0024
6024 Cytochrome P450 1A1 CYP1A1 0.0022
4924 Cytochrome P450 2C8 CYP2C8 0.0022
1374 Natriuretic peptides B NPPB 0.0019
1827 Gap junction alpha-1 protein GJA1 0.0019
1908 Vascular cell adhesion protein 1 VCAM1 0.0019
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0019
6432 Transporter snf 0.0018
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0017
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0017
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0017
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0017
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0017
1656 CYP2B protein CYP2B 0.0017
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0016
183 Vascular endothelial growth factor A VEGFA 0.0014
20 Prostaglandin G/H synthase 1 PTGS1 0.0014
233 Potassium channel subfamily K member 2 KCNK2 0.0014
6151 Monocarboxylate transporter 10 SLC16A10 0.0012
6106 Cytochrome P450 2C18 CYP2C18 0.0012
1360 Sphingomyelin phosphodiesterase SMPD1 0.0012
833 Organic cation/carnitine transporter 1 SLC22A4 0.0012
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0012
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0012
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0012
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0011
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0011
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0011
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0011
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0011
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0011
158 Sodium channel protein type 1 subunit alpha SCN1A 0.001
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0009
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0008
1618 High affinity nerve growth factor receptor NTRK1 0.0008
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0008
164 Histamine H4 receptor HRH4 0.0007
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0006
467 Delta-type opioid receptor OPRD1 0.0005
696 Kappa-type opioid receptor OPRK1 0.0005
1898 Cytochrome P450 1B1 CYP1B1 0.0004
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