DT-Web

DB00434 - Cyproheptadine


Identification
Name Cyproheptadine
Accession Number DB00434 (APRD00033)
Type small molecule
Description A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 287.3981
Groups approved
Monoisotopic Weight 287.167399677
Pharmacology
Indication For treatment of perennial and seasonal allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis due to inhalant allergens and foods, mild uncomplicated allergic skin manifestations of urticaria and angioedema, amelioration of allergic reactions to blood or plasma, cold urticaria, dermatographism, and as therapy for anaphylactic reactions adjunctive to epinephrine.
Mechanism of action Cyproheptadine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding. Cyproheptadine also competes with serotonin at receptor sites in smooth muscle in the intestines and other locations. Antagonism of serotonin on the appetite center of the hypothalamus may account for Cyproheptadine's ability to stimulate appetite.
Absorption Well absorbed after oral administration.
Protein binding 96 to 99%
Biotransformation Hepatic (cytochrome P-450 system) and some renal.
Route of elimination After a single 4 mg oral dose of14C-labelled cyproheptadine HCl in normal subjects, given as tablets 2% to 20% of the radioactivity was excreted in the stools. At least 40% of the administered radioactivity was excreted in the urine.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Donepezil Possible antagonism of action
Fluoxetine Possible antagonism of action
Galantamine Possible antagonism of action
Metyrapone This combination renders test invalid
Rivastigmine Possible antagonism of action
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Cyproheptadine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Triprolidine Triprolidine and Cyproheptadine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Trospium Trospium and Cyproheptadine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food Interactions
  • Take with food.
  • Avoid alcohol.

Targets


Histamine H1 receptor
Name Histamine H1 receptor
Gene Name HRH1
Pharmacological action yes
Actions antagonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.6186
5-hydroxytryptamine 2A receptor
Name 5-hydroxytryptamine 2A receptor
Gene Name HTR2A
Pharmacological action yes
Actions antagonist
References
  • Rashid M, Nakazawa M, Nagatomo T: Effects of sarpogrelate, a novel 5-HT2 antagonist, on 5-HT-induced endothelium-dependent relaxations in porcine coronary artery. Jpn J Pharmacol. 2002 Aug;89(4):405-12. - Pubmed
  • Honda M, Nishida T, Ono H: Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors. Eur J Pharmacol. 2003 Jan 1;458(1-2):91-9. - Pubmed
  • Callaway CW, Rempel N, Peng RY, Geyer MA: Serotonin 5-HT1-like receptors mediate hyperactivity in rats induced by 3,4-methylenedioxymethamphetamine. Neuropsychopharmacology. 1992 Sep;7(2):113-27. - Pubmed
  • Hoenicke EM, Vanecek SA, Woods JH: The discriminative stimulus effects of clozapine in pigeons: involvement of 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors. J Pharmacol Exp Ther. 1992 Oct;263(1):276-84. - Pubmed
  • Calka O, Metin A, Dulger H, Erkoc R: Effect of cyproheptadine on serum leptin levels. Adv Ther. 2005 Sep-Oct;22(5):424-8. - Pubmed
DTHybrid score 0.3143
5-hydroxytryptamine 2C receptor
Name 5-hydroxytryptamine 2C receptor
Gene Name HTR2C
Pharmacological action yes
Actions antagonist
References
  • Honda M, Nishida T, Ono H: Tricyclic analogs cyclobenzaprine, amitriptyline and cyproheptadine inhibit the spinal reflex transmission through 5-HT(2) receptors. Eur J Pharmacol. 2003 Jan 1;458(1-2):91-9. - Pubmed
DTHybrid score 0.2419
Muscarinic acetylcholine receptor M1
Name Muscarinic acetylcholine receptor M1
Gene Name CHRM1
Pharmacological action unknown
Actions antagonist
References
  • Eltze M, Lambrecht G, Mutschler E: Cyproheptadine displays high affinity for muscarinic receptors but does not discriminate between receptor subtypes. Eur J Pharmacol. 1989 Dec 7;173(2-3):219-22. - Pubmed
DTHybrid score 0.7392
Muscarinic acetylcholine receptor M2
Name Muscarinic acetylcholine receptor M2
Gene Name CHRM2
Pharmacological action unknown
Actions antagonist
References
  • Eltze M, Lambrecht G, Mutschler E: Cyproheptadine displays high affinity for muscarinic receptors but does not discriminate between receptor subtypes. Eur J Pharmacol. 1989 Dec 7;173(2-3):219-22. - Pubmed
DTHybrid score 0.6028
Muscarinic acetylcholine receptor M3
Name Muscarinic acetylcholine receptor M3
Gene Name CHRM3
Pharmacological action unknown
Actions antagonist
References
  • Eltze M, Lambrecht G, Mutschler E: Cyproheptadine displays high affinity for muscarinic receptors but does not discriminate between receptor subtypes. Eur J Pharmacol. 1989 Dec 7;173(2-3):219-22. - Pubmed
DTHybrid score 0.5839

Enzymes


UDP-glucuronosyltransferase 1-3
Name UDP-glucuronosyltransferase 1-3
Gene Name UGT1A3
Actions substrate
References
  • Green MD, King CD, Mojarrabi B, Mackenzie PI, Tephly TR: Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3. Drug Metab Dispos. 1998 Jun;26(6):507-12. - Pubmed
DTHybrid score 0.1623

Predictions


Id Partner name Gene Name Score
450 Muscarinic acetylcholine receptor M4 CHRM4 0.2943
274 Muscarinic acetylcholine receptor M5 CHRM5 0.2398
4119 Cytochrome P450 2D6 CYP2D6 0.238
4512 Cytochrome P450 3A4 CYP3A4 0.1831
831 D(2) dopamine receptor DRD2 0.1756
23 D(1A) dopamine receptor DRD1 0.1319
556 Alpha-1A adrenergic receptor ADRA1A 0.1266
1588 Multidrug resistance protein 1 ABCB1 0.1152
4200 Cytochrome P450 1A2 CYP1A2 0.1123
320 5-hydroxytryptamine 1A receptor HTR1A 0.1116
4757 Cytochrome P450 2C9 CYP2C9 0.1045
318 Alpha-2A adrenergic receptor ADRA2A 0.1011
436 5-hydroxytryptamine 2B receptor HTR2B 0.0964
824 Sodium-dependent serotonin transporter SLC6A4 0.0924
638 D(3) dopamine receptor DRD3 0.0858
432 D(4) dopamine receptor DRD4 0.0845
6016 Cytochrome P450 2C19 CYP2C19 0.081
632 Alpha-1B adrenergic receptor ADRA1B 0.079
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0764
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0735
4924 Cytochrome P450 2C8 CYP2C8 0.0735
378 Alpha-2C adrenergic receptor ADRA2C 0.0727
3923 Cholinesterase BCHE 0.0714
629 Alpha-2B adrenergic receptor ADRA2B 0.0706
716 5-hydroxytryptamine 7 receptor HTR7 0.0623
6030 Cytochrome P450 2B6 CYP2B6 0.0594
789 Alpha-1D adrenergic receptor ADRA1D 0.059
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0581
4118 Cytochrome P450 3A5 CYP3A5 0.0577
725 5-hydroxytryptamine 1D receptor HTR1D 0.0574
163 D(1B) dopamine receptor DRD5 0.0523
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0521
885 5-hydroxytryptamine 1B receptor HTR1B 0.0514
6013 Cytochrome P450 2E1 CYP2E1 0.0514
1256 5-hydroxytryptamine 6 receptor HTR6 0.0481
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0435
713 Sodium-dependent dopamine transporter SLC6A3 0.0424
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0401
6107 Cytochrome P450 3A7 CYP3A7 0.0397
6145 Solute carrier family 22 member 1 SLC22A1 0.037
341 5-hydroxytryptamine 3 receptor HTR3A 0.0351
587 Serum albumin ALB 0.0338
5718 Cytochrome P450 2A6 CYP2A6 0.033
833 Organic cation/carnitine transporter 1 SLC22A4 0.0287
528 5-hydroxytryptamine 1E receptor HTR1E 0.0277
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0271
6144 Solute carrier family 22 member 2 SLC22A2 0.0266
20 Prostaglandin G/H synthase 1 PTGS1 0.0264
118 Organic cation/carnitine transporter 2 SLC22A5 0.0264
124 Histamine H2 receptor HRH2 0.0258
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0247
6024 Cytochrome P450 1A1 CYP1A1 0.0238
94 5-hydroxytryptamine 4 receptor HTR4 0.0227
1656 CYP2B protein CYP2B 0.0219
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0218
70 Type-1 angiotensin II receptor AGTR1 0.0212
3802 Sodium channel protein type 2 subunit alpha SCN2A 0.0197
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0195
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0195
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.019
5880 Thrombopoietin receptor MPL 0.0183
696 Kappa-type opioid receptor OPRK1 0.0176
1341 Histamine H3 receptor HRH3 0.0175
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0174
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0172
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0172
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0171
1729 Solute carrier family 22 member 6 SLC22A6 0.0168
516 Neurotensin receptor type 2 NTSR2 0.0168
474 Acetylcholinesterase ACHE 0.0162
238 Peroxisome proliferator-activated receptor gamma PPARG 0.016
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.016
6432 Transporter snf 0.0156
2129 Sucrase-isomaltase, intestinal SI 0.0149
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0148
174 Sigma 1-type opioid receptor SIGMAR1 0.0146
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0145
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.014
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0136
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0128
131 Synaptic vesicular amine transporter SLC18A2 0.0127
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0126
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.0125
723 Cytosolic phospholipase A2 PLA2G4A 0.0124
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.012
465 Calmodulin CALM1 0.012
467 Delta-type opioid receptor OPRD1 0.0115
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.011
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0109
6106 Cytochrome P450 2C18 CYP2C18 0.0106
4164 Potassium voltage-gated channel subfamily KQT member 5 KCNQ5 0.0104
4163 Potassium voltage-gated channel subfamily KQT member 4 KCNQ4 0.0104
362 Melatonin receptor type 1B MTNR1B 0.0103
571 Melatonin receptor type 1A MTNR1A 0.0103
290 Prostaglandin G/H synthase 2 PTGS2 0.0098
3941 Amine oxidase [flavin-containing] A MAOA 0.0096
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.009
750 Voltage-dependent calcium channel gamma-1 subunit CACNG1 0.0089
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0088
1275 Estrogen sulfotransferase SULT1E1 0.0086
1629 Transcription factor AP-1 JUN 0.0084
6147 Solute carrier family 22 member 3 SLC22A3 0.0083
890 Niemann-Pick C1-like protein 1 NPC1L1 0.0082
847 Mu-type opioid receptor OPRM1 0.0081
164 Histamine H4 receptor HRH4 0.008
2164 Multidrug resistance-associated protein 4 ABCC4 0.008
4162 Potassium voltage-gated channel subfamily KQT member 3 KCNQ3 0.0079
6182 Cytochrome P450 2J2 CYP2J2 0.0078
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0076
923 Glutamate receptor 3 GRIA3 0.0075
1760 Aminopeptidase N ANPEP 0.0072
6843 Aminopeptidase N pepN 0.0072
117 Sterol O-acyltransferase 1 SOAT1 0.007
3876 Aromatic-L-amino-acid decarboxylase DDC 0.007
1360 Sphingomyelin phosphodiesterase SMPD1 0.0069
6179 UDP-glucuronosyltransferase 2B17 UGT2B17 0.0069
6102 Arylamine N-acetyltransferase 2 NAT2 0.0068
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0061
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0061
459 Retinoic acid receptor RXR-alpha RXRA 0.0061
193 Beta-1 adrenergic receptor ADRB1 0.006
766 Beta-2 adrenergic receptor ADRB2 0.0059
1630 Integrin beta-2 ITGB2 0.0056
6097 Protein S100-A2 S100A2 0.005
1810 Protein S100-A1 S100A1 0.005
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0049
1618 High affinity nerve growth factor receptor NTRK1 0.0048
921 Glutamate receptor 2 GRIA2 0.0047
6044 Serum paraoxonase/lactonase 3 PON3 0.0045
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0045
2021 Thrombomodulin THBD 0.0044
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0043
3426 Glutamine synthetase glnA 0.0043
3987 Glutamine synthetase GLUL 0.0043
1048 Protein S100-A13 S100A13 0.0043
2226 Protein S100-A12 S100A12 0.0043
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0042
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0042
904 Glutathione S-transferase P GSTP1 0.0042
572 Integrin alpha-L ITGAL 0.0042
776 Bile salt export pump ABCB11 0.0041
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0041
2132 Protein S100-B S100B 0.004
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.004
267 Plasminogen activator inhibitor 1 SERPINE1 0.004
6141 Sodium/bile acid cotransporter SLC10A1 0.0039
4122 Histone deacetylase 2 HDAC2 0.0038
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0038
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0037
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0037
1039 Histone deacetylase 9 HDAC9 0.0037
6221 Steroid hormone receptor ERR1 ESRRA 0.0036
811 Translocator protein TSPO 0.0036
862 Multidrug resistance-associated protein 1 ABCC1 0.0036
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0035
6217 High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B PDE8B 0.0035
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0034
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0033
1898 Cytochrome P450 1B1 CYP1B1 0.0032
380 Cytochrome P450 17A1 CYP17A1 0.0032
6220 Aryl hydrocarbon receptor AHR 0.0032
1457 Long-chain-fatty-acid--CoA ligase 4 ACSL4 0.0032
630 Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial ACADSB 0.0032
6142 Solute carrier family 22 member 8 SLC22A8 0.0032
182 2-oxoglutarate dehydrogenase E1 component, mitochondrial OGDH 0.0031
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.003
6216 High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A PDE8A 0.003
1792 Tissue-type plasminogen activator PLAT 0.003
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.003
841 Gamma-aminobutyric-acid receptor subunit alpha-6 GABRA6 0.003
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0029
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0029
530 Gamma-aminobutyric-acid receptor subunit alpha-4 GABRA4 0.0029
273 Apoptosis regulator Bcl-2 BCL2 0.0029
691 cAMP-specific 3',5'-cyclic phosphodiesterase 7B PDE7B 0.0029
3809 Estrogen-related receptor gamma ESRRG 0.0029
3939 Amine oxidase [flavin-containing] B MAOB 0.0028
6085 Fatty acid-binding protein, intestinal FABP2 0.0028
580 Gamma-aminobutyric-acid receptor subunit alpha-3 GABRA3 0.0028
523 Gamma-aminobutyric-acid receptor subunit alpha-5 GABRA5 0.0028
423 Gamma-aminobutyric-acid receptor subunit alpha-2 GABRA2 0.0028
170 Succinate semialdehyde dehydrogenase, mitochondrial ALDH5A1 0.0027
779 High-affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A PDE7A 0.0026
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0026
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0025
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0024
4109 cAMP-specific 3',5'-cyclic phosphodiesterase 4C PDE4C 0.0024
280 4-aminobutyrate aminotransferase, mitochondrial ABAT 0.0024
6136 Multidrug resistance-associated protein 5 ABCC5 0.0024
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0023
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0023
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0021
952 Dipeptidyl peptidase 4 DPP4 0.002
738 Monocarboxylate transporter 1 SLC16A1 0.002
1971 cAMP-specific 3',5'-cyclic phosphodiesterase 4A PDE4A 0.002
3811 Cytochrome P450 19A1 CYP19A1 0.0019
2358 cAMP-specific 3',5'-cyclic phosphodiesterase 4D PDE4D 0.0019
4203 Histamine N-methyltransferase HNMT 0.0019
1024 Solute carrier family 22 member 11 SLC22A11 0.0019
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.0018
6143 Solute carrier family 22 member 7 SLC22A7 0.0018
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0017
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0017
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0016
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0013
↑