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DB04890 - Bepotastine


Identification
Name Bepotastine
Accession Number DB04890
Type small molecule
Description Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. Bepotastine was approved in Japan for use in the treatment of allergic rhinitis and uriticaria/puritus in July 2000 and January 2002, respectively, and is marketed by Tanabe Seiyaku Co., Ltd. under the brand name Talion. It is available in oral and opthalmic dosage forms in Japan. The opthalmic solution is FDA approved since Sept 8, 2009 and is under the brand name Bepreve.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 388.888
Groups approved
Monoisotopic Weight 388.155370383
Pharmacology
Indication For the symptomatic treatment of itchy eyes (caused by IgE-induced mast cell degranulation) due to allergic conjunctivitis.
Mechanism of action Because of a type 1 hypersensitivity reaction cascade that is triggered by antigen exposure, allergic conjunctivitis occurs. Allergen exposure is followed by conjunctival mast cell degranulation and histamine released as a result of the formation of complementary IgE cross-links on the conjunctiva. Due to the release of histamine, symptoms such as itching can be observed. Bepotastine works to relieve itchy eyes by three primary mechanisms of action. It is a non-sedating, selective antagonist of the histamine 1 (H1) receptor, a mast cell stabilizer, and it suppresses the migration of eosinophils into inflamed tissues to prevent tissue damage and worsening of allergic inflammation of the conjunctiva.
Absorption Tmax, after single dose, opthalmic = 1.2 hours; Cmax, 1.5%, opthalmic dose = 7.3 ?1.9 ng/mL; After 24 hours post-installation, levels of bepotastine are below quantifiable limit of 2 ng/mL. Minimal systemic absorption with opthalmic dosage form.
Protein binding 55.4% mean plasma protein binding with 10 mg oral dose. Extent of protein binding is independent of plasma drug concentration.
Biotransformation Minimal metabolism via CYP enzymes
Route of elimination When a oral dose of 2.5 - 40 mg bepotastine is given, 75%-90% of the dose was excreted unchanged in the urine by 24 hours.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Histamine H1 receptor
Name Histamine H1 receptor
Gene Name HRH1
Pharmacological action yes
Actions antagonist
References
  • Andoh T, Kuraishi Y: Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice. Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64. Epub 2006 Jul 25. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.4747

Predictions


Id Partner name Gene Name Score
4119 Cytochrome P450 2D6 CYP2D6 0.0588
4512 Cytochrome P450 3A4 CYP3A4 0.0387
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0342
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0245
556 Alpha-1A adrenergic receptor ADRA1A 0.0245
502 5-hydroxytryptamine 2A receptor HTR2A 0.0224
4200 Cytochrome P450 1A2 CYP1A2 0.0215
4757 Cytochrome P450 2C9 CYP2C9 0.0198
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0188
713 Sodium-dependent dopamine transporter SLC6A3 0.0182
1588 Multidrug resistance protein 1 ABCB1 0.0177
1341 Histamine H3 receptor HRH3 0.0175
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0175
318 Alpha-2A adrenergic receptor ADRA2A 0.0172
450 Muscarinic acetylcholine receptor M4 CHRM4 0.017
6016 Cytochrome P450 2C19 CYP2C19 0.0169
590 5-hydroxytryptamine 2C receptor HTR2C 0.0169
516 Neurotensin receptor type 2 NTSR2 0.0168
6030 Cytochrome P450 2B6 CYP2B6 0.014
831 D(2) dopamine receptor DRD2 0.0135
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0132
23 D(1A) dopamine receptor DRD1 0.0118
824 Sodium-dependent serotonin transporter SLC6A4 0.0116
320 5-hydroxytryptamine 1A receptor HTR1A 0.0109
6013 Cytochrome P450 2E1 CYP2E1 0.0103
4118 Cytochrome P450 3A5 CYP3A5 0.0098
432 D(4) dopamine receptor DRD4 0.0098
632 Alpha-1B adrenergic receptor ADRA1B 0.0097
638 D(3) dopamine receptor DRD3 0.0086
1275 Estrogen sulfotransferase SULT1E1 0.0086
1656 CYP2B protein CYP2B 0.0084
6107 Cytochrome P450 3A7 CYP3A7 0.0082
4924 Cytochrome P450 2C8 CYP2C8 0.0079
378 Alpha-2C adrenergic receptor ADRA2C 0.0078
629 Alpha-2B adrenergic receptor ADRA2B 0.0078
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0076
716 5-hydroxytryptamine 7 receptor HTR7 0.0072
118 Organic cation/carnitine transporter 2 SLC22A5 0.0069
789 Alpha-1D adrenergic receptor ADRA1D 0.0063
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0061
6145 Solute carrier family 22 member 1 SLC22A1 0.0058
1256 5-hydroxytryptamine 6 receptor HTR6 0.0058
833 Organic cation/carnitine transporter 1 SLC22A4 0.0055
124 Histamine H2 receptor HRH2 0.0054
6144 Solute carrier family 22 member 2 SLC22A2 0.0051
6182 Cytochrome P450 2J2 CYP2J2 0.005
6097 Protein S100-A2 S100A2 0.005
1810 Protein S100-A1 S100A1 0.005
725 5-hydroxytryptamine 1D receptor HTR1D 0.0047
341 5-hydroxytryptamine 3 receptor HTR3A 0.0046
1729 Solute carrier family 22 member 6 SLC22A6 0.0043
1048 Protein S100-A13 S100A13 0.0043
2226 Protein S100-A12 S100A12 0.0043
5718 Cytochrome P450 2A6 CYP2A6 0.0042
2132 Protein S100-B S100B 0.004
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.004
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0037
528 5-hydroxytryptamine 1E receptor HTR1E 0.0036
6024 Cytochrome P450 1A1 CYP1A1 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
885 5-hydroxytryptamine 1B receptor HTR1B 0.0034
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0034
163 D(1B) dopamine receptor DRD5 0.0033
164 Histamine H4 receptor HRH4 0.0031
6216 High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A PDE8A 0.003
465 Calmodulin CALM1 0.003
436 5-hydroxytryptamine 2B receptor HTR2B 0.003
691 cAMP-specific 3',5'-cyclic phosphodiesterase 7B PDE7B 0.0029
6106 Cytochrome P450 2C18 CYP2C18 0.0028
779 High-affinity cAMP-specific 3',5'-cyclic phosphodiesterase 7A PDE7A 0.0026
6147 Solute carrier family 22 member 3 SLC22A3 0.0026
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0026
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0026
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0024
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0024
4109 cAMP-specific 3',5'-cyclic phosphodiesterase 4C PDE4C 0.0024
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0023
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0023
587 Serum albumin ALB 0.0021
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0021
6040 6-phosphogluconate dehydrogenase, decarboxylating PGD 0.0021
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0021
696 Kappa-type opioid receptor OPRK1 0.0021
1971 cAMP-specific 3',5'-cyclic phosphodiesterase 4A PDE4A 0.002
198 Sodium channel protein type 10 subunit alpha SCN10A 0.002
2358 cAMP-specific 3',5'-cyclic phosphodiesterase 4D PDE4D 0.0019
4203 Histamine N-methyltransferase HNMT 0.0019
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0019
20 Prostaglandin G/H synthase 1 PTGS1 0.0019
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.0018
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0018
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0018
6432 Transporter snf 0.0018
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0016
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0015
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0013
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0013
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0013
193 Beta-1 adrenergic receptor ADRB1 0.0013
766 Beta-2 adrenergic receptor ADRB2 0.0012
1360 Sphingomyelin phosphodiesterase SMPD1 0.0012
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0012
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0011
776 Bile salt export pump ABCB11 0.001
3923 Cholinesterase BCHE 0.0009
1618 High affinity nerve growth factor receptor NTRK1 0.0008
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0008
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0007
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0006
467 Delta-type opioid receptor OPRD1 0.0005
1898 Cytochrome P450 1B1 CYP1B1 0.0004
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