DT-Web

DB01148 - Flavoxate


Identification
Name Flavoxate
Accession Number DB01148 (APRD00972)
Type small molecule
Description A drug that has been used in various urinary syndromes and as an antispasmodic. Its therapeutic usefulness and its mechanism of action are not clear. It may have local anesthetic activity and direct relaxing effects on smooth muscle as well as some activity as a muscarinic antagonist. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 391.4596
Groups approved
Monoisotopic Weight 391.178358293
Pharmacology
Indication For symptomatic relief of dysuria, urgency, nocturia, suprapubic pain, frequency and incontinence as may occur in cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis.
Mechanism of action Flavoxate acts as a direct antagonist at muscarinic acetylcholine receptors in cholinergically innervated organs. Its anticholinergic-parasympatholytic action reduces the tonus of smooth muscle in the bladder, effectively reducing the number of required voids, urge incontinence episodes, urge severity and improving retention, facilitating increased volume per void.
Absorption Well absorbed from gastrointestinal tract.
Protein binding Not Available
Biotransformation Not Available
Route of elimination 57% of the flavoxate HCl was excreted in the urine within 24 hours.
Toxicity The oral LD50 for flavoxate HCl in rats is 4273 mg/kg. The oral LD50 for flavoxate HCl in mice is 1837 mg/kg. Symptoms of overdose include convulsions, decreased ability to sweat, (warm, red skin, dry mouth, and increased body temperature), hallucinations, increased heart rate and blood pressure, and mental confusion.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Donepezil Possible antagonism of action
Galantamine Possible antagonism of action
Rivastigmine Possible antagonism of action
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Flavoxate, 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.
Trimethobenzamide Trimethobenzamide and Flavoxate, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Triprolidine Triprolidine and Flavoxate, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trospium Trospium and Flavoxate, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food Interactions
  • Take without regard to meals.
  • Food may reduce irritation.

Targets


Muscarinic acetylcholine receptor M2
Name Muscarinic acetylcholine receptor M2
Gene Name CHRM2
Pharmacological action yes
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Greco KA, McVary KT: The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. - Pubmed
  • Uckert S, Stief CG, Odenthal KP, Truss MC, Lietz B, Jonas U: Responses of isolated normal human detrusor muscle to various spasmolytic drugs commonly used in the treatment of the overactive bladder. Arzneimittelforschung. 2000 May;50(5):456-60. - Pubmed
  • Abbiati GA, Ceserani R, Nardi D, Pietra C, Testa R: Receptor binding studies of the flavone, REC 15/2053, and other bladder spasmolytics. Pharm Res. 1988 Jul;5(7):430-3. - Pubmed
DTHybrid score 0.3968
Muscarinic acetylcholine receptor M1
Name Muscarinic acetylcholine receptor M1
Gene Name CHRM1
Pharmacological action yes
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Abbiati GA, Ceserani R, Nardi D, Pietra C, Testa R: Receptor binding studies of the flavone, REC 15/2053, and other bladder spasmolytics. Pharm Res. 1988 Jul;5(7):430-3. - Pubmed
DTHybrid score 0.5171

Predictions


Id Partner name Gene Name Score
51 Muscarinic acetylcholine receptor M3 CHRM3 0.2563
450 Muscarinic acetylcholine receptor M4 CHRM4 0.1509
274 Muscarinic acetylcholine receptor M5 CHRM5 0.1215
492 Histamine H1 receptor HRH1 0.0639
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0605
4119 Cytochrome P450 2D6 CYP2D6 0.0581
3923 Cholinesterase BCHE 0.05
4512 Cytochrome P450 3A4 CYP3A4 0.0434
502 5-hydroxytryptamine 2A receptor HTR2A 0.0368
831 D(2) dopamine receptor DRD2 0.0329
1588 Multidrug resistance protein 1 ABCB1 0.0294
556 Alpha-1A adrenergic receptor ADRA1A 0.0292
23 D(1A) dopamine receptor DRD1 0.0251
590 5-hydroxytryptamine 2C receptor HTR2C 0.0237
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0196
6016 Cytochrome P450 2C19 CYP2C19 0.0193
824 Sodium-dependent serotonin transporter SLC6A4 0.0185
4200 Cytochrome P450 1A2 CYP1A2 0.0169
4757 Cytochrome P450 2C9 CYP2C9 0.0166
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0161
789 Alpha-1D adrenergic receptor ADRA1D 0.0159
6013 Cytochrome P450 2E1 CYP2E1 0.0156
632 Alpha-1B adrenergic receptor ADRA1B 0.0147
833 Organic cation/carnitine transporter 1 SLC22A4 0.0138
320 5-hydroxytryptamine 1A receptor HTR1A 0.0136
432 D(4) dopamine receptor DRD4 0.0133
436 5-hydroxytryptamine 2B receptor HTR2B 0.0129
723 Cytosolic phospholipase A2 PLA2G4A 0.0124
4924 Cytochrome P450 2C8 CYP2C8 0.0124
124 Histamine H2 receptor HRH2 0.0122
6145 Solute carrier family 22 member 1 SLC22A1 0.0119
6030 Cytochrome P450 2B6 CYP2B6 0.0118
4118 Cytochrome P450 3A5 CYP3A5 0.0117
341 5-hydroxytryptamine 3 receptor HTR3A 0.0112
6024 Cytochrome P450 1A1 CYP1A1 0.0111
6144 Solute carrier family 22 member 2 SLC22A2 0.011
118 Organic cation/carnitine transporter 2 SLC22A5 0.0109
638 D(3) dopamine receptor DRD3 0.0109
318 Alpha-2A adrenergic receptor ADRA2A 0.0107
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0107
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0099
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0099
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0096
713 Sodium-dependent dopamine transporter SLC6A3 0.0096
2129 Sucrase-isomaltase, intestinal SI 0.0094
378 Alpha-2C adrenergic receptor ADRA2C 0.0092
629 Alpha-2B adrenergic receptor ADRA2B 0.0091
1656 CYP2B protein CYP2B 0.0087
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0086
528 5-hydroxytryptamine 1E receptor HTR1E 0.0083
474 Acetylcholinesterase ACHE 0.0079
1256 5-hydroxytryptamine 6 receptor HTR6 0.0077
163 D(1B) dopamine receptor DRD5 0.0075
5718 Cytochrome P450 2A6 CYP2A6 0.0073
716 5-hydroxytryptamine 7 receptor HTR7 0.007
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0065
725 5-hydroxytryptamine 1D receptor HTR1D 0.0062
885 5-hydroxytryptamine 1B receptor HTR1B 0.0061
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0059
6107 Cytochrome P450 3A7 CYP3A7 0.0059
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0053
465 Calmodulin CALM1 0.0047
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0045
6432 Transporter snf 0.0039
94 5-hydroxytryptamine 4 receptor HTR4 0.0036
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0036
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0033
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0033
380 Cytochrome P450 17A1 CYP17A1 0.0032
587 Serum albumin ALB 0.003
198 Sodium channel protein type 10 subunit alpha SCN10A 0.003
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0029
6106 Cytochrome P450 2C18 CYP2C18 0.0028
1360 Sphingomyelin phosphodiesterase SMPD1 0.0027
6147 Solute carrier family 22 member 3 SLC22A3 0.0027
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0027
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0025
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0024
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0024
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0019
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0019
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0019
1618 High affinity nerve growth factor receptor NTRK1 0.0019
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0018
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0018
3941 Amine oxidase [flavin-containing] A MAOA 0.0018
164 Histamine H4 receptor HRH4 0.0017
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0016
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0015
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0015
20 Prostaglandin G/H synthase 1 PTGS1 0.0014
193 Beta-1 adrenergic receptor ADRB1 0.0013
766 Beta-2 adrenergic receptor ADRB2 0.0012
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0012
467 Delta-type opioid receptor OPRD1 0.0012
696 Kappa-type opioid receptor OPRK1 0.0012
1898 Cytochrome P450 1B1 CYP1B1 0.001
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