PYRIDOSTIGMINE BROMIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H13N2O2.Br
Molecular Weight	261.116
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Br-].CN(C)C(=O)OC1=C[N+](C)=CC=C1

InChI

InChIKey=VNYBTNPBYXSMOO-UHFFFAOYSA-M

InChI=1S/C9H13N2O2.BrH/c1-10(2)9(12)13-8-5-4-6-11(3)7-8;/h4-7H,1-3H3;1H/q+1;/p-1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/15193s18lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21815707

Acquired myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction, characterized clinically by muscle weakness and abnormal fatigability on exertion. Current guidelines and recommendations for MG treatment are based largely on clinical experience, retrospective analyses and expert consensus. Pyridostigmine (under the trade names Mestinon (Valeant Pharmaceuticals)), has been used as a treatment for MG for over 50 years and is generally considered safe. It is suitable as a long-term treatment in patients with generalized non-progressive milder disease, and as an adjunctive therapy in patients with severe disease who are also receiving immunotherapy. Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft by competing with acetylcholine for attachment to acetylcholinesterase, thus slowing down the hydrolysis of acetylcholine, and thereby increases efficiency of cholinergic transmission in the neuromuscular junction and prolongs the effects of acetylcholine. The side effects of Mestinon are most commonly related to over dosage and generally are of two varieties, muscarinic and nicotinic. Among those in the former group are nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis and diaphoresis. Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness. Muscarinic side effects can usually be counteracted by atropine, but for reasons shown in the preceding section the expedient is not without danger. As with any compound containing the bromide radical, a skin rash may be seen in an occasional patient. Such reactions usually subside promptly upon discontinuance of the medication.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Acetylcholinesterase 207 Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10814558	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Myasthenia gravis 21 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/15193s18lbl.pdf	Primary		Approved 8429	MESTINON Approved Use Pyridostigmine bromide is useful in the treatment of myasthenia gravis. Launch Date 1955

C_max

Value	Dose	Co-administered	Analyte	Population
176.03 ng/mL EXPERIMENT https://www.tandfonline.com/doi/abs/10.1080/10826070701540605	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		PYRIDOSTIGMINE BROMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
819.999 ng × h/mL EXPERIMENT https://www.tandfonline.com/doi/abs/10.1080/10826070701540605	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		PYRIDOSTIGMINE BROMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
909.86 ng × h/mL EXPERIMENT https://www.tandfonline.com/doi/abs/10.1080/10826070701540605	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		PYRIDOSTIGMINE BROMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.787 h EXPERIMENT https://www.tandfonline.com/doi/abs/10.1080/10826070701540605	60 mg single, oral dose: 60 mg route of administration: Oral experiment type: SINGLE co-administered:		PYRIDOSTIGMINE BROMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
18.8% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12029383	single, unknown		PYRIDOSTIGMINE BROMIDE unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
180 mg 3 times / day multiple, oral MTD Dose: 180 mg, 3 times / day Route: oral Route: multiple Dose: 180 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18622640/	unhealthy, 18-67 years n = 10 Health Status: unhealthy Condition: autonomic neuropathy \| constipation Age Group: 18-67 years Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/18622640/	Sources: https://pubmed.ncbi.nlm.nih.gov/18622640/
160 mg 3 times / day multiple, oral Studied dose Dose: 160 mg, 3 times / day Route: oral Route: multiple Dose: 160 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18622640/	unhealthy, 18-67 years n = 10 Health Status: unhealthy Condition: autonomic neuropathy \| constipation Age Group: 18-67 years Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/18622640/	DLT: Diaphoresis, Sweating... Dose limiting toxicities: Diaphoresis (10%) Sweating (10%) Abdominal cramps (10%) Sources: https://pubmed.ncbi.nlm.nih.gov/18622640/
30 mg 3 times / day multiple, oral Recommended Dose: 30 mg, 3 times / day Route: oral Route: multiple Dose: 30 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2072481/	healthy, adult n = 41650 Health Status: healthy Age Group: adult Sex: M+F Population Size: 41650 Sources: https://pubmed.ncbi.nlm.nih.gov/2072481/	Disc. AE: Headache, Hypertension... AEs leading to discontinuation/dose reduction: Headache (0.002%) Hypertension (0.005%) Allergic reaction (0.005%) Bronchitis (0.007%) Nausea (0.05%) Diarrhea (0.05%) Sources: https://pubmed.ncbi.nlm.nih.gov/2072481/
900 mg 1 times / day single, oral Studied dose Dose: 900 mg, 1 times / day Route: oral Route: single Dose: 900 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1757242/	healthy, adult n = 1 Health Status: healthy Age Group: adult Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1757242/	Other AEs: Abdominal cramps, Diarrhea... Other AEs: Abdominal cramps Diarrhea Emesis Nausea Hypersalivation Urinary incontinence Muscle weakness Blurred vision Sources: https://pubmed.ncbi.nlm.nih.gov/1757242/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781 substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1054 CYP2D1 7

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/12642463/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.osti.gov/biblio/502657-metabolism-proposed-nerve-agent-pretreatment-pyridostigmine-bromide-final-report-december-december	no
CYP2C9 1037	substrate 3367 Sources: https://www.osti.gov/biblio/502657-metabolism-proposed-nerve-agent-pretreatment-pyridostigmine-bromide-final-report-december-december	no
CYP2D1 7	substrate 3367 Sources: https://www.osti.gov/biblio/502657-metabolism-proposed-nerve-agent-pretreatment-pyridostigmine-bromide-final-report-december-december	no
CYP2D6 1217	substrate 3367 Sources: https://www.osti.gov/biblio/502657-metabolism-proposed-nerve-agent-pretreatment-pyridostigmine-bromide-final-report-december-december	no
CYP3A4 1737	substrate 3367 Sources: https://www.osti.gov/biblio/502657-metabolism-proposed-nerve-agent-pretreatment-pyridostigmine-bromide-final-report-december-december	no

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY527196	https://www.001chemical.com/chem/155-97-5
Active Biopharma	ABP000290	http://www.activebiopharma.com/101-26-8
BLD Pharm	BD01091457	http://www.bldpharm.com/products/155-97-5.html
Boroncore	BC004003	http://www.boroncore.com/101-26-8.html
Finetech	FT-0696330	http://www.finetechnology-ind.com/prod/detail/pub/155-97-5.html
Molcore	MC527196	https://www.molcore.com/product/155-97-5
OChem	3113	http://www.ocheminc.com/index.php?act=psearch&pid=01M268
Parchem	60071	https://www.parchem.com/chemical-supplier-distributor/Pyridostigmine-060071.aspx
Smolecule	S594315	https://www.smolecule.com/products/s594315
THE BioTek	bt-459391	https://www.thebiotek.com/product/others/bt-459391
mcule	MCULE-2045762718	https://mcule.com/MCULE-2045762718/

PubMed

Title	Date	PubMed
Prognostic factors of thymectomy in patients with myasthenia gravis: a cohort of 132 patients.	2001	11721122
Familial autoimmune myasthenia gravis.	2001 Apr	11465320
Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single institution experience.	2001 Apr	11294402
Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin, alone and in combination.	2001 Apr	11248143
Chromatographic method for the determination of diazepam, pyridostigmine bromide, and their metabolites in rat plasma and urine.	2001 Apr 25	11339294
Induction of urinary excretion of 3-nitrotyrosine, a marker of oxidative stress, following administration of pyridostigmine bromide, DEET (N,N-diethyl-m-toluamide) and permethrin, alone and in combination in rats.	2001 Apr 30	11325563
Combination anticonvulsant treatment of soman-induced seizures.	2001 Dec	11920921
Self-reported exposures and their association with unexplained illness in a population-based case-control study of Gulf War veterans.	2001 Dec	11765675
Effects of contralateral white noise stimulation on distortion product otoacoustic emissions in myasthenic patients.	2001 Dec	11707354
A validated HPLC method for the determination of pyridostigmine bromide, acetaminophen, acetylsalicylic acid and caffeine in rat plasma and urine.	2001 Dec	11600306
Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects.	2001 Feb	11503945
Many Gulf War illnesses may be autoimmune disorders caused by the chemical and biological stressors pyridostigmine bromide, and adrenaline.	2001 Feb	11425278
Effects of thienylphencyclidine (TCP) on seizure activity and brain damage produced by soman in guinea-pigs: ECoG correlates of neurotoxicity.	2001 Feb	11307847
Pyridostigmine bromide and the long-term subjective health status of a sample of female reserve component Gulf War veterans: a brief report.	2001 Feb	11293048
Bulbar presentations of myasthenia gravis in the elderly patient.	2001 Jan	11233614
Myasthenia gravis during low-dose IFN-alpha therapy for chronic hepatitis C.	2001 Jul	11506739
Interaction of pyridostigmine and physical stress on antioxidant defense system in skeletal muscle of mice.	2001 Jul-Aug	11481669
Laryngeal myasthenia gravis: report of 40 cases.	2001 Mar	12269627
Impairment of GH responsiveness to GH-releasing hexapeptide (GHRP-6) in Prader-Willi syndrome.	2001 May	11407654
Myasthenia gravis with autoimmune autonomic neuropathy.	2001 May 14	11474561
The effects of pyridostigmine bromide, permethrin, and DEET alone, or in combination, on fixed-ratio and fixed-interval behavior in male and female rats.	2001 May-Jun	11420065
Fetal antigen 1 in healthy adults and patients with pituitary disease: relation to physiological, pathological, and pharmacological GH levels.	2001 Nov	11701723
Reactive oxygen species mediate pyridostigmine-induced neuronal apoptosis: involvement of muscarinic and NMDA receptors.	2001 Nov 15	11708896
Long-term evaluation of extended thymectomy with anterior mediastinal dissection for myasthenia gravis.	2001 Oct	11602911
The combined effects of pyridostigmine and chronic stress on brain cortical and blood acetylcholinesterase, corticosterone, prolactin and alternation performance in rats.	2001 Oct-Nov	11701190
Determination of depleted uranium, pyridostigmine bromide and its metabolite in plasma and urine following combined administration in rats.	2001 Sep	11470205
Disruption of the blood-brain barrier and neuronal cell death in cingulate cortex, dentate gyrus, thalamus, and hypothalamus in a rat model of Gulf-War syndrome.	2002 Aug	12270692
Altered hypothalamic cholinergic responses in patients with nonulcer dyspepsia: a study of pyridostigmine-stimulated growth hormone release.	2002 Aug	12190157
Locomotor and sensorimotor performance deficit in rats following exposure to pyridostigmine bromide, DEET, and permethrin. Alone and in combination.	2002 Aug	12151649
A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned rats and mice.	2002 Aug 15	12135621
Preparation and in vitro evaluation of pyridostigmine bromide microparticles.	2002 Aug 21	12176241
The use of the pyridostigmine growth hormone-releasing hormone stimulation test to detect growth hormone deficiency in patients with pituitary adenomas.	2002 Jan	11782869
Prevention and treatment of injury from chemical warfare agents.	2002 Jan 7	11856948
Presentation of myasthenia gravis mimicking blepharospasm.	2002 Jan 8	11781428
Physiological and performance effects of pyridostigmine bromide in healthy volunteers: a dose-response study.	2002 Jul	12110996
Sensitivity to vecuronium in seropositive and seronegative patients with myasthenia gravis.	2002 Jul	12088952
Pyridostigmine bromide and the long-term subjective health status of a sample of over 700 male Reserve Component Gulf War era veterans.	2002 Jun	12090498
[Growth disorders in Down's syndrome: growth hormone treatment].	2002 Jun	11961498
Pyridostigmine bromide modulates the dermal disposition of [14C]permethrin.	2002 Jun 15	12079425
Risk factors for multisymptom illness in US Army veterans of the Gulf War.	2002 Mar	11911029
Sensorimotor deficit and cholinergic changes following coexposure with pyridostigmine bromide and sarin in rats.	2002 Mar	11861982
Caramiphen and scopolamine prevent soman-induced brain damage and cognitive dysfunction.	2002 May	12164550
Review of the value of huperzine as pretreatment of organophosphate poisoning.	2002 May	12164543
Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin.	2002 May	12029383
Idiotypic mimicry of a catalytic antibody active site.	2002 Oct	12220886
In myasthenia gravis, clinical and immunological improvement post-thymectomy segregate with results of in vitro antibody secretion by immunocytes.	2002 Oct 15	12220697
Acute and repeated restraint stress have little effect on pyridostigmine toxicity or brain regional cholinesterase inhibition in rats.	2002 Sep	12215670
Complete inhibition of hypothalamic somatostatin activity is only partially responsible for the growth hormone response to strenuous exercise.	2002 Sep	12200751
Pharmacokinetic/pharmacodynamic modeling of rocuronium in myasthenic patients is improved by taking into account the number of unbound acetylcholine receptors.	2002 Sep	12198043
Gulf War related exposure factors influencing topical absorption of 14C-permethrin.	2002 Sep 5	12243864

Patents

Sample Use Guides

In Vivo Use Guide

Syrup: This form permits accurate dosage adjustment for children and "brittle" myasthenic patients who require fractions of 60 mg doses. It is more easily swallowed, especially in the morning, by patients with bulbar involvement. Timespan Tablets: This form provides uniformly slow release, hence prolonged duration of drug action; it facilitates control of myasthenic symptoms with fewer individual doses daily. The immediate effect of a 180 mg Timespan Tablet is about equal to that of a 60 mg Conventional Tablet; however, its duration of effectiveness, although varying in individual patients, averages 2½ times that of a 60 mg dose.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

PYRIDOSTIGMINE BROMIDE

Official Name

English

RO-1-5130

Code

English

PYRIDOSTIGMINE BROMIDE [MI]

Common Name

English

KALYMIN

Brand Name

English

PYRIDINIUM, 3-(((DIMETHYLAMINO)CARBONYL)OXY)-1-METHYL-, BROMIDE (1:1)

Systematic Name

English

PYRIDOSTIGMINE BROMIDE [ORANGE BOOK]

Common Name

English

NSC-679759

Code

English

PYRIDOSTIGMINI BROMIDUM [WHO-IP LATIN]

Common Name

English

PYRIDOSTIGMINE BROMIDE [JAN]

Common Name

English

REGONOL

Brand Name

English

PYRIDOSTIGMINE BROMIDE [MART.]

Common Name

English

PYRIDOSTIGMINE BROMIDE [EP IMPURITY]

Common Name

English

3-Hydroxy-1-methylpyridinium bromide dimethylcarbamate

Systematic Name

English

Pyridostigmine bromide [WHO-DD]

Common Name

English

PYRIDOSTIGMINE BROMIDE [EP MONOGRAPH]

Common Name

English

NSC-758435

Code

English

KALIMIN

Brand Name

English

PYRIDOSTIGMINE BROMIDE [WHO-IP]

Common Name

English

MESTINON

Brand Name

English

PYRIDINIUM, 3-(((DIMETHYLAMINO)CARBONYL)OXY)-1-METHYL-, BROMIDE

Systematic Name

English

PYRIDOSTIGMINE BROMIDE [HSDB]

Common Name

English

PYRIDOSTIGMINE BROMIDE [USP MONOGRAPH]

Common Name

English

PYRIDOSTIGMINE BROMIDE [USP-RS]

Common Name

English

pyridostigmine bromide [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47792