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

Stem definitionDrug idCAS RN
acetylcholinesterase inhibitors 1897 59-99-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • neostigmine
  • eustigmin
  • eustigmine
  • prostigmin
  • prostigmine
  • vagostigmine
  • neostigmine methylsulfate
  • neostigmine bromide
A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.
  • Molecular weight: 223.30
  • Formula: C12H19N2O2
  • CLOGP: -2.81
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 0
  • TPSA: 29.54
  • ALOGS: -3.58
  • ROTB: 3
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
60 mg O
2 mg P
0.40 ml None
40 mg ointment

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 100 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 67 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.12 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 2 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.74 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 9.20 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.30 hours Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 1 % Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -2.710 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.018 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.230 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 2.742 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 96.180 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 95.050 % High 1
herg hERG pIC50 4.363 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 0.861 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 2.951 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 91.890 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,ITK,JAK1,JAK2,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CB,PIK3CG,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1 49
kinase-selectivity-class ACVR2B,AXL,BRAF,CSF1R,DDR1,EPHB4,ERBB2,GRK2,MAPK7,PDK4,SIK2,STK33 12
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.975 High 1
mh-clint Mouse hepatocyte intrinsic clearance 7.962 High 1
mppb Mouse plasma protein binding (% unbound) 96.090 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.327 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 95.460 % High 1
rh-clint Rat hepatocyte intrinsic clearance 4.732 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 97.460 % High 1
rppb Rat plasma protein binding (% unbound) 95.560 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 907.821 uM High 1

Approvals:

DateAgencyCompanyOrphan
May 31, 2013 FDA ECLAT PHARMS LLC

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
Vascular encephalopathy 96.73 31.12 17 2483 753 90625194
Subileus 91.37 31.12 21 2479 3623 90622324
Schizencephaly 73.78 31.12 12 2488 331 90625616
Cerebral haemorrhage foetal 73.61 31.12 12 2488 336 90625611
Serotonin syndrome 71.93 31.12 30 2470 37857 90588090
Gastrointestinal sounds abnormal 66.65 31.12 17 2483 4526 90621421
Neuromuscular block prolonged 66.08 31.12 12 2488 640 90625307
Ileus 63.81 31.12 22 2478 16524 90609423
Negative pressure pulmonary oedema 57.89 31.12 8 2492 69 90625878
Stress cardiomyopathy 56.36 31.12 19 2481 13336 90612611
Dystonia 55.82 31.12 20 2480 16799 90609148
Abdominal tenderness 54.56 31.12 17 2483 9307 90616640
Hypotension 54.11 31.12 55 2445 325342 90300605
Faecaloma 52.69 31.12 17 2483 10414 90615533
Atrioventricular dissociation 48.96 31.12 8 2492 227 90625720
Apnoea 46.15 31.12 15 2485 9399 90616548
Procedural hypertension 46.06 31.12 8 2492 330 90625617
Cardiac arrest 43.19 31.12 30 2470 104905 90521042
Anaphylactic reaction 43.17 31.12 28 2472 87496 90538451
Pulmonary oedema 41.18 31.12 24 2476 62056 90563891
Brachial plexopathy 40.99 31.12 7 2493 261 90625686
Necrotising colitis 40.52 31.12 9 2491 1329 90624618
Dementia 38.99 31.12 17 2483 23844 90602103
Abdominal distension 37.33 31.12 30 2470 130571 90495376
White blood cell count increased 36.85 31.12 23 2477 67218 90558729
Bladder disorder 36.45 31.12 13 2487 10759 90615188
Myopia 32.16 31.12 8 2492 1924 90624023
Delayed recovery from anaesthesia 31.59 31.12 7 2493 1023 90624924
Chorea 31.46 31.12 8 2492 2102 90623845

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
Serotonin syndrome 118.80 34.39 41 1380 25804 42594110
Bradycardia 108.63 34.39 54 1367 85430 42534484
Cardiac arrest 88.01 34.39 51 1370 109269 42510645
Drug interaction 62.39 34.39 59 1362 266940 42352974
Metabolic acidosis 51.95 34.39 28 1393 51830 42568084
Pseudomonal sepsis 50.52 34.39 14 1407 4235 42615679
Renal ischaemia 47.25 34.39 11 1410 1659 42618255
Accelerated idioventricular rhythm 41.90 34.39 7 1414 188 42619726
Appendicitis perforated 39.69 34.39 10 1411 2096 42617818
Hyperthermia malignant 37.38 34.39 10 1411 2648 42617266
Atrioventricular block second degree 37.22 34.39 11 1410 4176 42615738
Acute pulmonary oedema 36.85 34.39 13 1408 8638 42611276
Angle closure glaucoma 34.98 34.39 8 1413 1114 42618800

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
Serotonin syndrome 140.16 27.04 59 3878 59094 110526268
Bradycardia 118.80 27.04 72 3865 155445 110429917
Cardiac arrest 110.42 27.04 75 3862 196678 110388684
Vascular encephalopathy 91.22 27.04 17 3920 807 110584555
Subileus 74.16 27.04 21 3916 6416 110578946
Pulmonary oedema 70.14 27.04 44 3893 100615 110484747
Neuromuscular block prolonged 66.62 27.04 14 3923 1233 110584129
Drug interaction 63.11 27.04 83 3854 500100 110085262
Gastrointestinal sounds abnormal 57.61 27.04 17 3920 6001 110579361
Ileus 57.55 27.04 26 3911 30703 110554659
Hypotension 57.11 27.04 81 3856 523768 110061594
Stress cardiomyopathy 55.63 27.04 21 3916 15785 110569577
Laryngospasm 52.74 27.04 15 3922 4653 110580709
Dystonia 52.05 27.04 23 3914 25782 110559580
Tachycardia 51.34 27.04 51 3886 226594 110358768
Apnoea 51.20 27.04 19 3918 13620 110571742
Abdominal tenderness 45.47 27.04 17 3920 12440 110572922
White blood cell count increased 45.10 27.04 33 3904 96809 110488553
Negative pressure pulmonary oedema 44.05 27.04 9 3928 690 110584672
Procedural hypertension 43.76 27.04 8 3929 341 110585021
Delayed recovery from anaesthesia 43.41 27.04 11 3926 2204 110583158
Renal ischaemia 42.89 27.04 11 3926 2312 110583050
Atrioventricular dissociation 42.79 27.04 8 3929 386 110584976
Hyperthermia malignant 41.67 27.04 12 3925 3888 110581474
Faecaloma 39.06 27.04 16 3921 14892 110570470
Accelerated idioventricular rhythm 38.60 27.04 7 3930 285 110585077
Brachial plexopathy 38.28 27.04 7 3930 299 110585063
Atrioventricular block second degree 36.69 27.04 13 3924 8168 110577194
Anaphylactic reaction 36.11 27.04 31 3906 114269 110471093
Necrotising colitis 35.75 27.04 9 3928 1756 110583606
Atrioventricular block complete 34.48 27.04 16 3921 20066 110565296
Acute pulmonary oedema 33.79 27.04 15 3922 16981 110568381
Appendicitis perforated 33.57 27.04 10 3927 3642 110581720
Abdominal distension 33.47 27.04 36 3901 175067 110410295
Metabolic acidosis 33.45 27.04 28 3909 99716 110485646
Cholinergic syndrome 33.08 27.04 8 3929 1324 110584038
Bladder disorder 32.79 27.04 13 3924 11124 110574238
Pseudomonal sepsis 31.76 27.04 12 3925 9034 110576328
Dementia 30.28 27.04 17 3920 31656 110553706
Post procedural complication 30.18 27.04 16 3921 26642 110558720
Intestinal pseudo-obstruction 30.03 27.04 9 3928 3347 110582015
Non-cardiogenic pulmonary oedema 29.92 27.04 8 3929 1976 110583386
Angle closure glaucoma 29.66 27.04 9 3928 3490 110581872
Myopia 28.85 27.04 8 3929 2263 110583099
Respiratory failure 27.45 27.04 36 3901 215296 110370066

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N07AA01 NERVOUS SYSTEM
OTHER NERVOUS SYSTEM DRUGS
PARASYMPATHOMIMETICS
Anticholinesterases
ATC N07AA51 NERVOUS SYSTEM
OTHER NERVOUS SYSTEM DRUGS
PARASYMPATHOMIMETICS
Anticholinesterases
ATC S01EB06 SENSORY ORGANS
OPHTHALMOLOGICALS
ANTIGLAUCOMA PREPARATIONS AND MIOTICS
Parasympathomimetics
FDA MoA N0000000177 Cholinesterase Inhibitors
MeSH PA D002800 Cholinesterase Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D010277 Parasympathomimetics
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018678 Cholinergic Agents
FDA EPC N0000175723 Cholinesterase Inhibitor
CHEBI has role CHEBI:35480 analgesic
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:38462 EC 3.1.1.7 (acetylcholinesterase) inhibitor
CHEBI has role CHEBI:39456 antiglaucoma drug
CHEBI has role CHEBI:55324 gastrointestinal drug
CHEBI has role CHEBI:74518 anti-obesity agent
CHEBI has role CHEBI:74530 antidote to curare poisoning
CHEBI has role CHEBI:231911 renoprotective agent
CHEBI has role CHEBI:37733 EC 3.1.1.8 (cholinesterase) inhibitor

Related Drugs by ATC class:

N07AA Anticholinesterases 3 drugs
ambenoniumdistigminepyridostigmine
S01EB Parasympathomimetics 9 drugs
aceclidineacetylcholinecarbacholdemecariumechothiophatefluostigmineparaoxonphysostigminepilocarpine

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

DiseaseRelationSNOMED_IDDOID
Myasthenia gravis indication 91637004 DOID:437
Reversal of neuromuscular blockade indication 241703000
Retention of urine indication 267064002
Urinary tract obstruction contraindication 7163005 DOID:5200
Peptic ulcer contraindication 13200003 DOID:750
Increased gastric tonus contraindication 18644006
Hyperthyroidism contraindication 34486009 DOID:7998
Conduction disorder of the heart contraindication 44808001
Peritonitis contraindication 48661000
Sinus bradycardia contraindication 49710005
Coronary occlusion contraindication 63739005
Gastrointestinal obstruction contraindication 126765001
Seizure disorder contraindication 128613002
Asthma contraindication 195967001 DOID:2841
Macrocolon contraindication 367495003
Gastrointestinal hypomotility contraindication 421807004
Increased Bronchial Secretions contraindication
Colonic Necrosis contraindication




🐶 Veterinary Drug Use

SpeciesUseRelation
Cattle Rumen atony Indication
Cattle Initiating peristalsis which causes evacuation of the bowel Indication
Cattle Emptying the urinary bladder Indication
Cattle Stimulating skeletal muscle contractions Indication
Cattle Antagonizes the effect of curare Indication
Horses Rumen atony Indication
Horses Initiating peristalsis which causes evacuation of the bowel Indication
Horses Emptying the urinary bladder Indication
Horses Stimulating skeletal muscle contractions Indication
Horses Antagonizes the effect of curare Indication
Sheep Rumen atony Indication
Sheep Initiating peristalsis which causes evacuation of the bowel Indication
Sheep Emptying the urinary bladder Indication
Sheep Stimulating skeletal muscle contractions Indication
Sheep Antagonizes the effect of curare Indication
Swine Rumen atony Indication
Swine Initiating peristalsis which causes evacuation of the bowel Indication
Swine Emptying the urinary bladder Indication
Swine Stimulating skeletal muscle contractions Indication
Swine Antagonizes the effect of curare Indication

🐶 Veterinary products

ProductApplicantIngredients
Stiglyn 1:500 Intervet Inc. 1

Acid dissociation constants calculated using MoKa v3.0.0

None

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
Acetylcholinesterase Enzyme INHIBITOR IC50 7.59 WOMBAT-PK CHEMBL
Cholinesterase Enzyme IC50 7.22 CHEMBL
Acetylcholinesterase Enzyme IC50 8.34 CHEMBL
Acetylcholinesterase Enzyme IC50 7.46 CHEMBL
Acetylcholinesterase Enzyme Ki 6 CHEMBL
Cholinesterase Enzyme IC50 7.15 CHEMBL

External reference:

IDSource
4019856 VUID
N0000147942 NUI
D00995 KEGG_DRUG
51-60-5 SECONDARY_CAS_RN
4017784 VANDF
4017785 VANDF
4019856 VANDF
C0027679 UMLSCUI
CHEMBL278020 ChEMBL_ID
DB01400 DRUGBANK_ID
CHEMBL211471 ChEMBL_ID
CHEMBL54126 ChEMBL_ID
D009388 MESH_DESCRIPTOR_UI
4456 PUBCHEM_CID
8993 IUPHAR_LIGAND_ID
114-80-7 SECONDARY_CAS_RN
3982TWQ96G UNII
262500 RXNORM
3968 MMSL
5165 MMSL
5166 MMSL
72417 MMSL
9863 MMSL
d00313 MMSL
001703 NDDF
001704 NDDF
001705 NDDF
373346001 SNOMEDCT_US
387294009 SNOMEDCT_US
80024007 SNOMEDCT_US
87151005 SNOMEDCT_US
CHEBI:7514 CHEBI
401 INN_ID
3982TWQ96G INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
NEOSTIGMINE METHYLSULFATE HUMAN PRESCRIPTION DRUG LABEL 1 0548-9601 INJECTION 0.50 mg INTRAVENOUS ANDA 16 sections
NEOSTIGMINE METHYLSULFATE HUMAN PRESCRIPTION DRUG LABEL 1 0548-9602 INJECTION 1 mg INTRAVENOUS ANDA 16 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 0641-6149 INJECTION 1 mg INTRAVENOUS ANDA 24 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 0641-6150 INJECTION 0.50 mg INTRAVENOUS ANDA 24 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 0641-6264 INJECTION 0.50 mg INTRAVENOUS ANDA 24 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 0641-6265 INJECTION 1 mg INTRAVENOUS ANDA 24 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 0641-6277 INJECTION 1 mg INTRAVENOUS ANDA 24 sections
NEOSTIGMINE METHYLSULFATE Human Prescription Drug Label 1 14445-413 INJECTION 0.50 mg INTRAVENOUS ANDA 24 sections
NEOSTIGMINE METHYLSULFATE Human Prescription Drug Label 1 14445-414 INJECTION 1 mg INTRAVENOUS ANDA 24 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 23155-517 INJECTION 0.50 mg INTRAVENOUS ANDA 23 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 23155-518 INJECTION 1 mg INTRAVENOUS ANDA 23 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 25021-610 INJECTION, SOLUTION 0.50 mg INTRAVENOUS ANDA 28 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 25021-611 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 28 sections
neostigmine methylsulfate Human Prescription Drug Label 1 31722-994 INJECTION 0.50 mg INTRAVENOUS ANDA 24 sections
neostigmine methylsulfate Human Prescription Drug Label 1 31722-995 INJECTION 1 mg INTRAVENOUS ANDA 24 sections
NEOSTIGMINE METHYLSULFATE HUMAN PRESCRIPTION DRUG LABEL 1 42023-188 INJECTION 0.50 mg INTRAVENOUS ANDA 23 sections
NEOSTIGMINE METHYLSULFATE HUMAN PRESCRIPTION DRUG LABEL 1 42023-189 INJECTION 1 mg INTRAVENOUS ANDA 23 sections
PREVDUO Human Prescription Drug Label 2 42023-269 INJECTION 1 mg INTRAVENOUS NDA 25 sections
Neostigmine HUMAN PRESCRIPTION DRUG LABEL 1 43598-528 INJECTION 0.50 mg INTRAVENOUS ANDA 24 sections
Neostigmine HUMAN PRESCRIPTION DRUG LABEL 1 43598-529 INJECTION 1 mg INTRAVENOUS ANDA 24 sections
Neostigmine Methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 43598-945 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 26 sections
NEOSTIGMINE METHYLSULFATE HUMAN PRESCRIPTION DRUG LABEL 1 50090-4532 INJECTION 1 mg INTRAVENOUS ANDA 17 sections
Neostigmine methylsulfate HUMAN PRESCRIPTION DRUG LABEL 1 50090-5197 INJECTION 0.50 mg INTRAVENOUS ANDA 25 sections
NEOSTIGMINE METHYLSULFATE HUMAN PRESCRIPTION DRUG LABEL 1 51662-1557 INJECTION 1 mg INTRAVENOUS ANDA 16 sections
Bloxiverz HUMAN PRESCRIPTION DRUG LABEL 1 51754-1200 INJECTION 1 mg INTRAVENOUS NDA 25 sections
Bloxiverz HUMAN PRESCRIPTION DRUG LABEL 1 51754-1210 INJECTION 0.50 mg INTRAVENOUS NDA 25 sections
Bloxiverz HUMAN PRESCRIPTION DRUG LABEL 1 51754-1220 INJECTION 1 mg INTRAVENOUS NDA 25 sections
Bloxiverz HUMAN PRESCRIPTION DRUG LABEL 1 51754-1240 INJECTION 1 mg INTRAVENOUS NDA 26 sections
Bloxiverz HUMAN PRESCRIPTION DRUG LABEL 1 51754-1240 INJECTION 1 mg INTRAVENOUS NDA 26 sections
NEOSTIGMINE METHYLSULFATE Human Prescription Drug Label 1 55150-348 INJECTION 0.50 mg INTRAVENOUS ANDA 24 sections