procyclidine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
muscarinic receptors agonists/antagonists 2276 77-37-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • procyclidine
  • kemadrine
  • tricoloid
  • tricyclamol
  • procyclidine hydrochloride
  • procyclidine HCl
A muscarinic antagonist that crosses the blood-brain barrier and is used in the treatment of drug-induced extrapyramidal disorders and in parkinsonism.
  • Molecular weight: 287.45
  • Formula: C19H29NO
  • CLOGP: 4.59
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 1
  • TPSA: 23.47
  • ALOGS: -4.47
  • ROTB: 5
  • Status: OFM
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
25 mg O
25 mg P

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 1.16 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 0.74 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.86 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 12 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 30 mg/mL Bocci G, Oprea TI, Benet LZ
fu (Fraction unbound in plasma) 0.09 % Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K
BA (Bioavailability) 75 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 1.939 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.156 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 28.510 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 11.324 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 19.200 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 39.780 % High 1
herg hERG pIC50 5.293 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 3.540 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 14.997 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 27.780 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT1,AKT2,AKT3,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK2,JAK3,MAP3K7,MAPK10,MAPK12,MAPK7,MAPKAPK2,MET,NTRK2,PDK2,PDK4,PDPK1,PIM2,PRKDC,SIK2,SIK3,TEK,TGFBR1 38
kinase-selectivity-class AXL,GRK2,PDK4 3
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 0.573 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.351 High 1
mh-clint Mouse hepatocyte intrinsic clearance 75.858 High 1
mppb Mouse plasma protein binding (% unbound) 21.050 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.807 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 38.910 % High 1
rat-kpuu-brain Rat brain Kpuu 0.337 % High 1
rh-clint Rat hepatocyte intrinsic clearance 200.909 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 49.650 % High 1
rppb Rat plasma protein binding (% unbound) 27.820 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 826.038 uM High 1

Approvals:

DateAgencyCompanyOrphan
July 27, 1955 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Schizophrenia 1136.13 63.08 269 8721 14645 90604812
Jaundice cholestatic 614.48 63.08 152 8838 9891 90609566
Hypomania 612.17 63.08 148 8842 8749 90610708
Psychotic disorder 609.59 63.08 193 8797 31037 90588420
Cholelithiasis 588.81 63.08 214 8776 52292 90567165
Blood bilirubin increased 370.14 63.08 145 8845 43325 90576132
Hepatotoxicity 362.67 63.08 145 8845 45697 90573760
Asthma-chronic obstructive pulmonary disease overlap syndrome 313.85 63.08 77 8913 4822 90614635
Total lung capacity increased 311.97 63.08 77 8913 4944 90614513
Sarcoidosis 254.46 63.08 77 8913 10596 90608861
Nasal polyps 253.00 63.08 77 8913 10803 90608654
Rhinitis allergic 220.20 63.08 77 8913 16708 90602749
Gastric pH decreased 218.90 63.08 43 8947 943 90618514
Cardiac murmur 214.13 63.08 77 8913 18117 90601340
Bronchiectasis 198.76 63.08 77 8913 22253 90597204
Cogwheel rigidity 191.80 63.08 44 8946 2058 90617399
Derealisation 190.02 63.08 41 8949 1444 90618013
H1N1 influenza 188.37 63.08 43 8947 1967 90617490
Depersonalisation/derealisation disorder 180.64 63.08 40 8950 1592 90617865
Feeling of despair 168.44 63.08 43 8947 3161 90616296
Lung neoplasm malignant 158.48 63.08 67 8923 24206 90595251
Neuroleptic malignant syndrome 155.76 63.08 58 8932 15038 90604419
Vomiting 155.07 63.08 278 8712 788015 89831442
Drooling 153.53 63.08 43 8947 4503 90614954
Muscle disorder 149.98 63.08 44 8946 5435 90614022
Dystonia 149.66 63.08 58 8932 16761 90602696
Feeling of body temperature change 148.65 63.08 44 8946 5605 90613852
Muscle rigidity 147.72 63.08 55 8935 14254 90605203
Hallucinations, mixed 142.53 63.08 43 8947 5846 90613611
Menstrual disorder 140.78 63.08 43 8947 6095 90613362
Dissociation 136.97 63.08 43 8947 6672 90612785
Paralysis 136.61 63.08 49 8941 11429 90608028
Chronic obstructive pulmonary disease 135.99 63.08 87 8903 73742 90545715
Parosmia 130.69 63.08 42 8948 7027 90612430
Incontinence 129.09 63.08 49 8941 13386 90606071
Pneumonia 122.58 63.08 223 8767 637836 89981621
Therapeutic product ineffective 120.06 63.08 31 8959 2383 90617074
Mania 112.63 63.08 45 8945 14079 90605378
Premature labour 108.00 63.08 43 8947 13333 90606124
Serotonin syndrome 107.39 63.08 59 8931 37828 90581629
Emotional disorder 106.62 63.08 44 8946 14953 90604504
Hypoaesthesia oral 104.94 63.08 44 8946 15556 90603901
Mydriasis 103.19 63.08 43 8947 14969 90604488
Hepatic enzyme increased 97.18 63.08 147 8843 360589 90258868
Feeling jittery 95.57 63.08 41 8949 15330 90604127
Sensory loss 92.34 63.08 42 8948 18033 90601424
Urinary retention 91.34 63.08 53 8937 37691 90581766
Nightmare 90.97 63.08 44 8946 21681 90597776
Dyskinesia 90.27 63.08 52 8938 36482 90582975
Mood swings 89.94 63.08 43 8947 20659 90598798
Restless legs syndrome 89.56 63.08 44 8946 22426 90597031
Cyanosis 89.39 63.08 42 8948 19413 90600044
Pallor 88.08 63.08 50 8940 34115 90585342
Agitation 83.19 63.08 62 8928 67036 90552421
Drug withdrawal syndrome 82.13 63.08 45 8945 28678 90590779
Blood sodium decreased 78.23 63.08 43 8947 27570 90591887
Restlessness 73.01 63.08 45 8945 35675 90583782
Speech disorder 72.39 63.08 49 8941 45536 90573921
Disorientation 71.45 63.08 48 8942 44066 90575391
Pain 71.18 63.08 8 8982 996333 89623124
Swollen tongue 67.32 63.08 47 8943 45909 90573548
Skin discolouration 66.50 63.08 46 8944 44269 90575188
Rash 66.48 63.08 3 8987 796097 89823360
Tinnitus 65.29 63.08 45 8945 43057 90576400
Limb injury 65.17 63.08 40 8950 31468 90587989

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Sedation 144.01 34.54 59 2702 30416 42588158
Tardive dyskinesia 122.55 34.54 36 2725 6888 42611686
Orthostatic hypotension 94.74 34.54 44 2717 30526 42588048
Neuroleptic malignant syndrome 89.32 34.54 38 2723 21434 42597140
Dystonia 78.66 34.54 30 2731 12760 42605814
Obesity 71.33 34.54 30 2731 16429 42602145
Aggression 63.37 34.54 38 2723 44125 42574449
Hallucination, auditory 57.49 34.54 25 2736 14839 42603735
Red blood cell sedimentation rate decreased 53.34 34.54 10 2751 265 42618309
Neglect of personal appearance 50.38 34.54 10 2751 360 42618214
Vitamin B complex deficiency 47.34 34.54 10 2751 492 42618082
Blood prolactin increased 45.29 34.54 13 2748 2285 42616289
Neutrophil count increased 41.88 34.54 22 2739 19782 42598792
Blood folate decreased 41.74 34.54 10 2751 871 42617703
Schizophrenia 41.62 34.54 18 2743 10532 42608042
Intestinal pseudo-obstruction 36.70 34.54 11 2750 2244 42616330
Pseudoporphyria 36.22 34.54 8 2753 486 42618088
Mental impairment 35.85 34.54 17 2744 12300 42606274
Slow speech 34.71 34.54 10 2751 1780 42616794
Irritability 34.70 34.54 22 2739 28106 42590468

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Schizophrenia 1084.99 41.88 283 11357 21543 110556116
Hypomania 592.83 41.88 150 11490 10060 110567599
Psychotic disorder 582.21 41.88 214 11426 50723 110526936
Jaundice cholestatic 557.98 41.88 154 11486 14454 110563205
Cholelithiasis 550.57 41.88 218 11422 63204 110514455
Total lung capacity increased 315.95 41.88 79 11561 5033 110572626
Hepatotoxicity 315.10 41.88 147 11493 63253 110514406
Asthma-chronic obstructive pulmonary disease overlap syndrome 299.02 41.88 79 11561 6265 110571394
Blood bilirubin increased 289.81 41.88 147 11493 75825 110501834
Neuroleptic malignant syndrome 246.89 41.88 103 11537 33956 110543703
Sarcoidosis 245.60 41.88 79 11561 12500 110565159
Nasal polyps 241.86 41.88 79 11561 13121 110564538
Rhinitis allergic 218.19 41.88 79 11561 17843 110559816
Gastric pH decreased 214.46 41.88 43 11597 987 110576672
Dystonia 203.82 41.88 83 11557 25722 110551937
Cardiac murmur 193.78 41.88 79 11561 24549 110553110
Muscle rigidity 175.21 41.88 73 11567 23958 110553701
Derealisation 172.33 41.88 41 11599 2117 110575542
H1N1 influenza 168.44 41.88 43 11597 2975 110574684
Depersonalisation/derealisation disorder 166.72 41.88 40 11600 2141 110575518
Cogwheel rigidity 164.49 41.88 44 11596 3654 110574005
Bronchiectasis 163.96 41.88 79 11561 36414 110541245
Feeling of despair 158.64 41.88 43 11597 3755 110573904
Menstrual disorder 148.82 41.88 43 11597 4741 110572918
Lung neoplasm malignant 145.22 41.88 71 11569 33771 110543888
Feeling of body temperature change 142.10 41.88 44 11596 6144 110571515
Drooling 140.00 41.88 45 11595 7094 110570565
Muscle disorder 138.84 41.88 44 11596 6628 110571031
Vomiting 135.35 41.88 296 11344 910379 109667280
Hallucinations, mixed 127.41 41.88 44 11596 8649 110569010
Paralysis 122.55 41.88 50 11590 15550 110562109
Premature labour 121.29 41.88 43 11597 9129 110568530
Dissociation 118.33 41.88 43 11597 9799 110567860
Therapeutic product ineffective 115.89 41.88 31 11609 2573 110575086
Incontinence 112.77 41.88 48 11592 16587 110561072
Hepatic enzyme increased 111.01 41.88 152 11488 320740 110256919
Chronic obstructive pulmonary disease 109.08 41.88 91 11549 109067 110468592
Parosmia 102.69 41.88 42 11598 13138 110564521
Mania 102.49 41.88 48 11592 20748 110556911
Serotonin syndrome 100.96 41.88 68 11572 59085 110518574
Hypoaesthesia oral 98.76 41.88 44 11596 16958 110560701
Emotional disorder 97.67 41.88 43 11597 16117 110561542
Dyskinesia 97.16 41.88 63 11577 51383 110526276
Feeling jittery 94.92 41.88 41 11599 14681 110562978
Sedation 90.92 41.88 68 11572 69615 110508044
Pneumonia 89.51 41.88 247 11393 876467 109701192
Mood swings 89.36 41.88 45 11595 22767 110554892
Mydriasis 84.72 41.88 43 11597 22114 110555545
Restless legs syndrome 83.26 41.88 44 11596 24582 110553077
Sensory loss 83.09 41.88 42 11598 21415 110556244
Urinary retention 73.56 41.88 60 11580 69623 110508036
Neglect of personal appearance 72.67 41.88 15 11625 399 110577260
Drug withdrawal syndrome 70.37 41.88 46 11594 38008 110539651
Cyanosis 70.25 41.88 42 11598 29699 110547960
Agitation 67.87 41.88 71 11569 112980 110464679
Nightmare 67.07 41.88 45 11595 38818 110538841
Pallor 66.82 41.88 52 11588 56415 110521244
Swollen tongue 65.88 41.88 53 11587 60309 110517350
Blood sodium decreased 65.25 41.88 44 11596 38275 110539384
Disorientation 62.57 41.88 55 11585 70616 110507043
Pain 61.26 41.88 13 11627 954942 109622717
Skin discolouration 59.85 41.88 46 11594 49000 110528659
Restlessness 58.44 41.88 48 11592 56211 110521448
Suicidal ideation 56.38 41.88 59 11581 93878 110483781
Speech disorder 54.67 41.88 48 11592 61521 110516138
Gastrooesophageal reflux disease 54.35 41.88 80 11560 179896 110397763
Limb injury 54.21 41.88 39 11601 37597 110540062
Eye pain 52.57 41.88 43 11597 50056 110527603
Aphasia 52.39 41.88 46 11594 58951 110518708
Tardive dyskinesia 50.88 41.88 26 11614 13553 110564106
Toxicity to various agents 49.41 41.88 136 11504 480419 110097240
Tinnitus 49.40 41.88 45 11595 60495 110517164
Rash 49.02 41.88 13 11627 820951 109756708
Disturbance in attention 48.48 41.88 45 11595 61950 110515709
Condition aggravated 47.31 41.88 177 11463 734659 109843000
Swelling face 45.02 41.88 52 11588 92269 110485390
Salivary hypersecretion 44.81 41.88 26 11614 17395 110560264
Tachycardia 42.01 41.88 81 11559 226564 110351095

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N04AA04 NERVOUS SYSTEM
ANTI-PARKINSON DRUGS
ANTICHOLINERGIC AGENTS
Tertiary amines
FDA MoA N0000175370 Cholinergic Antagonists
FDA EPC N0000175574 Anticholinergic
MeSH PA D000978 Antiparkinson Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018678 Cholinergic Agents
MeSH PA D018680 Cholinergic Antagonists
MeSH PA D018726 Anti-Dyskinesia Agents
MeSH PA D018727 Muscarinic Antagonists
CHEBI has role CHEBI:48407 antiparkinson drug
CHEBI has role CHEBI:48876 muscarinic antagonist
CHEBI has role CHEBI:66956 antidyskinesia agent

Related Drugs by ATC class:

N04AA Tertiary amines 9 drugs
biperidenbornaprinedexetimidemazaticolmetixenephenglutarimideprofenaminetrihexyphenidyltropatepine

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Postencephalitic parkinsonism indication 19972008 DOID:14332
Parkinsonism indication 32798002
Parkinson's disease indication 49049000 DOID:14330
Extrapyramidal disease indication 76349003
Arteriosclerotic Parkinsonism indication
Brain damage contraindication 2470005
Tachyarrhythmia contraindication 6285003
Urinary tract obstruction contraindication 7163005 DOID:5200
Severe chronic ulcerative colitis contraindication 14311001
Toxic megacolon contraindication 28536002 DOID:1770
Atony of colon contraindication 29479008
Hyperthyroidism contraindication 34486009 DOID:7998
Hypertensive disorder contraindication 38341003 DOID:10763
Complete trisomy 21 syndrome contraindication 41040004 DOID:14250
Achalasia of esophagus contraindication 45564002 DOID:9164
Chronic heart failure contraindication 48447003
Paralytic ileus contraindication 55525008 DOID:8442
Peptic reflux disease contraindication 57643001
Ulcerative colitis contraindication 64766004 DOID:8577
Drug AND/OR toxin-induced diarrhea contraindication 65979008
Spastic paralysis contraindication 78403003
Disturbance of salivary secretion contraindication 78948009
Hiatal hernia contraindication 84089009 DOID:12642
Kidney disease contraindication 90708001 DOID:557
Myasthenia gravis contraindication 91637004 DOID:437
Gastrointestinal obstruction contraindication 126765001
Autonomic dysreflexia contraindication 129618003
Bleeding contraindication 131148009
Myocardial dysfunction contraindication 233928007
Disease of liver contraindication 235856003 DOID:409
Bladder outflow obstruction contraindication 236645006
Pyloric obstruction contraindication 244815007
Benign prostatic hyperplasia contraindication 266569009
Retention of urine contraindication 267064002
Drowsy contraindication 271782001
Angle-closure glaucoma contraindication 392291006 DOID:13550
Gastric ulcer contraindication 397825006 DOID:10808
Chronic lung disease contraindication 413839001
Disorder of coronary artery contraindication 414024009




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.34 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Muscarinic acetylcholine receptor M1 GPCR ANTAGONIST Ki 8.34 PDSP CHEMBL
Muscarinic acetylcholine receptor M2 GPCR Ki 7.60 PDSP
Muscarinic acetylcholine receptor M3 GPCR Ki 7.91 PDSP
Muscarinic acetylcholine receptor M4 GPCR Ki 8.16 PDSP
Muscarinic acetylcholine receptor M5 GPCR Ki 7.62 PDSP
Glutamate [NMDA] receptor Ion channel Ki 5.77 CHEMBL
Histamine H1 receptor GPCR IC50 5.17 CHEMBL

External reference:

IDSource
4019907 VUID
N0000147992 NUI
D00782 KEGG_DRUG
4018767 VANDF
4019907 VANDF
C0033254 UMLSCUI
CHEBI:8448 CHEBI
CHEMBL86715 ChEMBL_ID
DB00387 DRUGBANK_ID
CHEMBL2110635 ChEMBL_ID
CHEMBL1761 ChEMBL_ID
D011352 MESH_DESCRIPTOR_UI
4919 PUBCHEM_CID
7280 IUPHAR_LIGAND_ID
224 INN_ID
60-48-0 SECONDARY_CAS_RN
1508-76-5 SECONDARY_CAS_RN
C6QE1Q1TKR UNII
142443 RXNORM
5364 MMSL
d00969 MMSL
001643 NDDF
004666 NDDF
387199007 SNOMEDCT_US
387247001 SNOMEDCT_US
44990002 SNOMEDCT_US
C6QE1Q1TKR INXIGHT DRUGS

Pharmaceutical products:

None