STRYCHNINE NITRATE

US Previously Marketed

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H22N2O2.HNO3
Molecular Weight	397.4244
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[N+]([O-])=O.[H][C@]12C[C@@]3([H])C4=CCO[C@@]5([H])CC(=O)N6C7=C(C=CC=C7)[C@@]1(CCN2C4)[C@]6([H])[C@@]35[H]

InChI

InChIKey=PCGVPMHGSJFFTI-ZEYGOCRCSA-N

InChI=1S/C21H22N2O2.HNO3/c24-18-10-16-19-13-9-17-21(6-7-22(17)11-12(13)5-8-25-16)14-3-1-2-4-15(14)23(18)20(19)21;2-1(3)4/h1-5,13,16-17,19-20H,6-11H2;(H,2,3,4)/t13-,16-,17-,19-,20-,21+;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/mesh/68013331
Curator's Comment: Description was created based on several sources, including http://www.merckvetmanual.com/mvm/toxicology/strychnine_poisoning/overview_of_strychnine_poisoning.html https://www.ncbi.nlm.nih.gov/pubmed/440838

Strychnine is an indole alkaloid obtained from the seeds of the Indian tree Strychnos nux-vomica. It gets its scientific name “strychnos” from Carl Linnaeus, who classified it back in 1753, but it was known to the population of India way before then. Nux vomica originates in India. Strychnine-containing baits are currently labelled for below-ground use and are intended for the control of pocket gophers. Their use as indoor pesticides has been eliminated since 1989. In the past, strychnine has been used as a pesticide to control rats, moles, gophers, and coyotes. Strychnine is highly toxic to most domestic animals. Strychnine is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glycine receptor (alpha-1/beta) 15 Target ID: CHEMBL2363052 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25146769	Antagonist 2778		0.62 µM [EC50]
Glycine receptor subunit alpha-1 24 Target ID: CHEMBL5845 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25146769	Antagonist 2778		0.16 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Nonketotic hyperglycinemia 11 Sources: https://www.ncbi.nlm.nih.gov/pubmed/440838 https://www.ncbi.nlm.nih.gov/pubmed/344282 https://www.ncbi.nlm.nih.gov/pubmed/541222	Primary		Preclinical	Unknown Approved Use Unknown
Sleep apnea 11 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7221350	Primary		Basic research	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
250 mg single, oral Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15483758	unknown, 46 years n = 1 Health Status: unknown Age Group: 46 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/15483758	Other AEs: Violent, Convulsions generalized... Other AEs: Violent (severe) Convulsions generalized (severe) Sources: https://pubmed.ncbi.nlm.nih.gov/15483758
15 g single, oral Dose: 15 g Route: oral Route: single Dose: 15 g Sources: https://jamanetwork.com/journals/jama/article-abstract/280892	unknown, 60 years n = 1 Health Status: unknown Age Group: 60 years Sex: M Population Size: 1 Sources: https://jamanetwork.com/journals/jama/article-abstract/280892	Other AEs: Nausea, Vomiting... Other AEs: Nausea (severe) Vomiting (severe) Sources: https://jamanetwork.com/journals/jama/article-abstract/280892

AEs

AE	Significance	Dose	Population
Convulsions generalized	severe	250 mg single, oral Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15483758	unknown, 46 years n = 1 Health Status: unknown Age Group: 46 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/15483758
Violent	severe	250 mg single, oral Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15483758	unknown, 46 years n = 1 Health Status: unknown Age Group: 46 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/15483758
Nausea	severe	15 g single, oral Dose: 15 g Route: oral Route: single Dose: 15 g Sources: https://jamanetwork.com/journals/jama/article-abstract/280892	unknown, 60 years n = 1 Health Status: unknown Age Group: 60 years Sex: M Population Size: 1 Sources: https://jamanetwork.com/journals/jama/article-abstract/280892
Vomiting	severe	15 g single, oral Dose: 15 g Route: oral Route: single Dose: 15 g Sources: https://jamanetwork.com/journals/jama/article-abstract/280892	unknown, 60 years n = 1 Health Status: unknown Age Group: 60 years Sex: M Population Size: 1 Sources: https://jamanetwork.com/journals/jama/article-abstract/280892

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	UGT1A4 347 UGT2B10 127 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/abs/pii/S1674638412600057	yes [IC50 5.9 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/29883892/	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://www.sciencedirect.com/science/article/abs/pii/S1674638412600057	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29234368/ \| https://pubmed.ncbi.nlm.nih.gov/21351573/	yes
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28803208/ \| https://issx.confex.com/issx/ap11/webprogram/Paper23904.html	yes
UGT2B10 127	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28803208/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/30545237/ \| https://pubmed.ncbi.nlm.nih.gov/30282042/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28973	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28973
MolPort	MolPort-001-742-519	https://www.molport.com/shop/molecule-link/MolPort-001-742-519
ZINC	ZINC000000119434	http://zinc15.docking.org/substances/ZINC000000119434
eMolecules	29541143	https://www.emolecules.com/cgi-bin/more?vid=29541143
eMolecules	29909187	https://www.emolecules.com/cgi-bin/more?vid=29909187
eMolecules	510211	https://www.emolecules.com/cgi-bin/more?vid=510211

PubMed

Title	Date	PubMed
Strychnos nux-vomica extract and its ultra-high dilution reduce voluntary ethanol intake in rats.	2001 Apr	11327524
Acute exposure to trichloroethylene differentially alters the susceptibility to chemoconvulsants in mice.	2001 Apr 12	11311456
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate.	2001 Apr 27	11328963
Anticonvulsant activities of the FS-1 subfraction isolated from roots of Delphinium denudatum.	2001 Aug	11507736
Centrally administered corticotropin-releasing hormone and peripheral injections of strychnine hydrochloride potentiate the acoustic startle response in preweanling rats.	2001 Dec	11770058
NMDA receptor-dependent periodic oscillations in cultured spinal cord networks.	2001 Dec	11731558
GABAergic and glycinergic neural inhibition in excitatory frequency tuning of bat inferior collicular neurons.	2001 Dec	11715077
The effect of proteolytic enzymes on the alpha9-nicotinic receptor-mediated response in isolated frog vestibular hair cells.	2001 Feb	11223279
Mu opiates inhibit long-term potentiation induction in the spinal cord slice.	2001 Feb	11160487
Neither GABA(A) nor strychnine-sensitive glycine receptors are the sole mediators of MAC for isoflurane.	2001 Jan	11133613
The generation of rhythmic activity in dissociated cultures of rat spinal cord.	2001 Jul	11553272
Enflurane actions on spinal cords from mice that lack the beta3 subunit of the GABA(A) receptor.	2001 Jul	11465553
Transition from GABAergic to glycinergic synaptic transmission in newly formed spinal networks.	2001 Jul	11431527
Glycine is taken up through GLYT1 and GLYT2 transporters into mouse spinal cord axon terminals and causes vesicular and carrier-mediated release of its proposed co-transmitter GABA.	2001 Mar	11259500
Coadministration of intrathecal strychnine and bicuculline effects synergistic allodynia in the rat: an isobolographic analysis.	2001 Mar	11181903
Subunit composition of strychnine-sensitive glycine receptors expressed by adult rat basolateral amygdala neurons.	2001 Oct	11683900
Excitatory synaptic currents in lumbosacral parasympathetic preganglionic neurons elicited from the lateral funiculus.	2001 Oct	11600622
[Arsenic and strychnine against tired eyes].	2001 Oct 10	11699263
The release of spinal prostaglandin E2 and the effect of nitric oxide synthetase inhibition during strychnine-induced allodynia.	2001 Sep	11524348
Osmoregulation of vasopressin secretion via activation of neurohypophysial nerve terminals glycine receptors by glial taurine.	2001 Sep 15	11549721
Sensitive and specific multiresidue methods for the determination of pesticides of various classes in clinical and forensic toxicology.	2001 Sep 15	11516896
Approaches to the synthesis of (+/-)-strychnine via the cobalt-mediated [2 + 2 + 2] cycloaddition: rapid assembly of a classic framework.	2001 Sep 26	11562215
Glycine receptors involved in synaptic transmission are selectively regulated by the cytoskeleton in mouse spinal neurons.	2002 Jan	11784780
Identification of two novel Drosophila melanogaster histamine-gated chloride channel subunits expressed in the eye.	2002 Jan 18	11714703

Patents

Sample Use Guides

In Vivo Use Guide

daily dosage of 0.2 to 0.9 mg/kg, given orally in four doses

Route of Administration: Oral

In Vitro Use Guide

Glycine-evoked (500 um) currents were blocked by strychnine (IC50 = 630 nm) in human pluripotent stem cell-derived excitatory cortical neurones.

Name

Type

Language

STRYCHNINE NITRATE

Common Name

English

STRYCHNINE NITRATE [MART.]

Common Name

English

STRYCHNINUM NITRICUM [HPUS]

Common Name

English

STRYCHNIDIN-10-ONE, NITRATE (1:1)

Common Name

English

STRYCHNINE NITRATE [MI]

Common Name

English

STRYCHNINUM NITRICUM

Common Name

English

Strychnine nitrate [WHO-DD]

Common Name

English

STRYCHNINE, MONONITRATE

Common Name

English

Code System Code Type Description

DAILYMED

O642E96711