DT-Web

DB00376 - Trihexyphenidyl


Identification
Name Trihexyphenidyl
Accession Number DB00376 (APRD00070)
Type small molecule
Description One of the centrally acting muscarinic antagonists used for treatment of parkinsonian disorders and drug-induced extrapyramidal movement disorders and as an antispasmodic. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 301.4662
Groups approved
Monoisotopic Weight 301.240564619
Pharmacology
Indication Indicated for the treatment of parkinson's disease and extrapyramidal reactions caused by drugs.
Mechanism of action Trihexyphenidyl is a selective M1 muscarinic acetylcholine receptor antagonist. It is able to discriminate between the M1 (cortical or neuronal) and the peripheral muscarinic subtypes (cardiac and glandular). Trihexyphenidyl partially blocks cholinergic activity in the CNS, which is responsible for the symptoms of Parkinson's disease. It is also thought to increase the availability of dopamine, a brain chemical that is critical in the initiation and smooth control of voluntary muscle movement.
Absorption Trihexyphenidyl is rapidly absorbed from the gastrointestinal tract.
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity Symptoms of overdose include mydriasis, dryness of mucous membranes, red face, atonic states of bowels and bladder, and hyperthermia in high doses. Central consequences are agitation, confusion, and hallucinations. An untreated overdose may be fatal, particular in children. Premortal signs are respiratory depression and cardiac arrest.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Donepezil Possible antagonism of action
Galantamine Possible antagonism of action
Haloperidol The anticholinergic increases the risk of psychosis and tardive dyskinesia
Potassium Chloride The ulcerative effects of solid oral dosage forms of KCl may be enhanced by Trihexyphenidyl, an anticholinergic. Anticholinergics slow gastric emptying, increasing the contact time between the gastrointestinal mucosa and KCl. Prolonged exposure to KCl increases the risk of gastric and intestinal irritation and ulceration. Solid oral dosage forms of KCl should be avoided; alternatives include liquid or effervescent potassium preparations.
Pramlintide The anticholinergic effects of Trihexyphenidyl may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
Rivastigmine Possible antagonism of action
Secretin The stimulatory effect of Secretin may be reduced by anticholinergics such as Trihexyphenidyl. Concomitant use of Secretin and drugs with substantial anticholinergic effects should be avoided. If combination therapy must be used, Secretin efficacy should be closely monitored.
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trihexyphenidyl, 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 Trihexyphenidyl, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Triprolidine Triprolidine and Trihexyphenidyl, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trospium Trospium and Trihexyphenidyl, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food Interactions Not Available

Targets


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
  • Prus AJ, Pehrson AL, Philibin SD, Wood JT, Vunck SA, Porter JH: The role of M1 muscarinic cholinergic receptors in the discriminative stimulus properties of N-desmethylclozapine and the atypical antipsychotic drug clozapine in rats. Psychopharmacology (Berl). 2009 Apr;203(2):295-301. Epub 2008 Aug 7. - Pubmed
  • Giachetti A, Giraldo E, Ladinsky H, Montagna E: Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine. Br J Pharmacol. 1986 Sep;89(1):83-90. - Pubmed
  • Tanda G, Katz JL: Muscarinic preferential M(1) receptor antagonists enhance the discriminative-stimulus effects of cocaine in rats. Pharmacol Biochem Behav. 2007 Oct;87(4):400-4. Epub 2007 Jun 2. - Pubmed
  • Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. - Pubmed
  • Freedman SB, Beer MS, Harley EA: Muscarinic M1, M2 receptor binding. Relationship with functional efficacy. Eur J Pharmacol. 1988 Oct 26;156(1):133-42. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.8625
Muscarinic acetylcholine receptor M2
Name Muscarinic acetylcholine receptor M2
Gene Name CHRM2
Pharmacological action unknown
Actions antagonist
References
  • Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H: A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8. - Pubmed
  • Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. - Pubmed
  • Freedman SB, Beer MS, Harley EA: Muscarinic M1, M2 receptor binding. Relationship with functional efficacy. Eur J Pharmacol. 1988 Oct 26;156(1):133-42. - Pubmed
DTHybrid score 0.7545
Muscarinic acetylcholine receptor M3
Name Muscarinic acetylcholine receptor M3
Gene Name CHRM3
Pharmacological action unknown
Actions antagonist
References
  • Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H: A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8. - Pubmed
  • Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. - Pubmed
  • Freedman SB, Beer MS, Harley EA: Muscarinic M1, M2 receptor binding. Relationship with functional efficacy. Eur J Pharmacol. 1988 Oct 26;156(1):133-42. - Pubmed
DTHybrid score 0.7578
Muscarinic acetylcholine receptor M4
Name Muscarinic acetylcholine receptor M4
Gene Name CHRM4
Pharmacological action unknown
Actions antagonist
References
  • Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H: A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8. - Pubmed
  • Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. - Pubmed
DTHybrid score 0.5385
Muscarinic acetylcholine receptor M5
Name Muscarinic acetylcholine receptor M5
Gene Name CHRM5
Pharmacological action unknown
Actions antagonist
References
  • Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H: A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8. - Pubmed
  • Dorje F, Wess J, Lambrecht G, Tacke R, Mutschler E, Brann MR: Antagonist binding profiles of five cloned human muscarinic receptor subtypes. J Pharmacol Exp Ther. 1991 Feb;256(2):727-33. - Pubmed
DTHybrid score 0.4382

Predictions


Id Partner name Gene Name Score
492 Histamine H1 receptor HRH1 0.1453
4119 Cytochrome P450 2D6 CYP2D6 0.1343
4512 Cytochrome P450 3A4 CYP3A4 0.1117
502 5-hydroxytryptamine 2A receptor HTR2A 0.0985
556 Alpha-1A adrenergic receptor ADRA1A 0.0839
1588 Multidrug resistance protein 1 ABCB1 0.0799
3923 Cholinesterase BCHE 0.0794
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0764
831 D(2) dopamine receptor DRD2 0.0735
590 5-hydroxytryptamine 2C receptor HTR2C 0.0685
23 D(1A) dopamine receptor DRD1 0.0597
4200 Cytochrome P450 1A2 CYP1A2 0.0552
6016 Cytochrome P450 2C19 CYP2C19 0.0541
789 Alpha-1D adrenergic receptor ADRA1D 0.0539
4757 Cytochrome P450 2C9 CYP2C9 0.0536
540 Sodium-dependent noradrenaline transporter SLC6A2 0.051
632 Alpha-1B adrenergic receptor ADRA1B 0.0501
432 D(4) dopamine receptor DRD4 0.0452
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0441
824 Sodium-dependent serotonin transporter SLC6A4 0.043
6013 Cytochrome P450 2E1 CYP2E1 0.0418
6030 Cytochrome P450 2B6 CYP2B6 0.0389
638 D(3) dopamine receptor DRD3 0.037
320 5-hydroxytryptamine 1A receptor HTR1A 0.0364
318 Alpha-2A adrenergic receptor ADRA2A 0.0327
4924 Cytochrome P450 2C8 CYP2C8 0.0323
2129 Sucrase-isomaltase, intestinal SI 0.0317
378 Alpha-2C adrenergic receptor ADRA2C 0.0312
629 Alpha-2B adrenergic receptor ADRA2B 0.0309
4118 Cytochrome P450 3A5 CYP3A5 0.0296
528 5-hydroxytryptamine 1E receptor HTR1E 0.0281
341 5-hydroxytryptamine 3 receptor HTR3A 0.027
833 Organic cation/carnitine transporter 1 SLC22A4 0.0267
1256 5-hydroxytryptamine 6 receptor HTR6 0.0261
163 D(1B) dopamine receptor DRD5 0.0255
436 5-hydroxytryptamine 2B receptor HTR2B 0.0245
716 5-hydroxytryptamine 7 receptor HTR7 0.0237
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0229
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0229
6145 Solute carrier family 22 member 1 SLC22A1 0.0223
6144 Solute carrier family 22 member 2 SLC22A2 0.0218
725 5-hydroxytryptamine 1D receptor HTR1D 0.021
885 5-hydroxytryptamine 1B receptor HTR1B 0.0206
118 Organic cation/carnitine transporter 2 SLC22A5 0.0193
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.018
6107 Cytochrome P450 3A7 CYP3A7 0.0167
124 Histamine H2 receptor HRH2 0.0163
465 Calmodulin CALM1 0.0159
5718 Cytochrome P450 2A6 CYP2A6 0.0151
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0136
6432 Transporter snf 0.0133
6024 Cytochrome P450 1A1 CYP1A1 0.013
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0127
723 Cytosolic phospholipase A2 PLA2G4A 0.0124
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.012
587 Serum albumin ALB 0.0102
713 Sodium-dependent dopamine transporter SLC6A3 0.0096
6106 Cytochrome P450 2C18 CYP2C18 0.0095
1360 Sphingomyelin phosphodiesterase SMPD1 0.0093
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0093
6147 Solute carrier family 22 member 3 SLC22A3 0.0092
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0091
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0088
1656 CYP2B protein CYP2B 0.0087
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0086
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0082
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0081
474 Acetylcholinesterase ACHE 0.0079
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0065
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0064
1618 High affinity nerve growth factor receptor NTRK1 0.0064
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0064
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0062
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0061
467 Delta-type opioid receptor OPRD1 0.0059
696 Kappa-type opioid receptor OPRK1 0.0058
164 Histamine H4 receptor HRH4 0.0057
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0054
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0049
20 Prostaglandin G/H synthase 1 PTGS1 0.0047
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0045
193 Beta-1 adrenergic receptor ADRB1 0.0043
766 Beta-2 adrenergic receptor ADRB2 0.0042
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0042
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
1898 Cytochrome P450 1B1 CYP1B1 0.0033
380 Cytochrome P450 17A1 CYP17A1 0.0032
198 Sodium channel protein type 10 subunit alpha SCN10A 0.003
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0029
6182 Cytochrome P450 2J2 CYP2J2 0.0028
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0022
847 Mu-type opioid receptor OPRM1 0.0018
3941 Amine oxidase [flavin-containing] A MAOA 0.0018
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0015
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