STRYCHNINE GLYCEROPHOSPHATE

US Previously Marketed

First marketed in 1921

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
Early expression of glycine and GABA(A) receptors in developing spinal cord neurons. Effects on neurite outgrowth.	2001	11738262
The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea.	2001	11686898
Expression and function of glycine receptors in striatal cholinergic interneurons from rat and mouse.	2001	11457589
Superimposition-based protocol as a tool for determining bioactive conformations. I. Application to ligands of the glycinergic receptor (GlyR).	2001	11449572
Slow inhibitory potentials in the teleost Mauthner cell.	2001	11246169
Interactions between allosteric modulators and 4-DAMP and other antagonists at muscarinic receptors: potential significance of the distance between the N and carboxyl C atoms in the molecules of antagonists.	2001 Apr	11495349
An expert system for automated structure elucidation utilizing 1H-1H, 13C-1H and 15N-1H 2D NMR correlations.	2001 Apr	11371077
Nux vomica 30 prepared with and without succession shows antialcoholic effect on toads and distinctive molecular association.	2001 Apr	11341461
Strychnos nux-vomica extract and its ultra-high dilution reduce voluntary ethanol intake in rats.	2001 Apr	11327524
Bitter taste transduced by PLC-beta(2)-dependent rise in IP(3) and alpha-gustducin-dependent fall in cyclic nucleotides.	2001 Apr	11245589
Acute exposure to trichloroethylene differentially alters the susceptibility to chemoconvulsants in mice.	2001 Apr 12	11311456
Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 12-2001. A 16-year-old boy with an altered mental status and muscle rigidity.	2001 Apr 19	11309639
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate.	2001 Apr 27	11328963
Reversal of chloroquine and mefloquine resistance in Plasmodium falciparum by the two monoindole alkaloids, icajine and isoretuline.	2001 Aug	11509972
Biogenetically inspired approach to the Strychnos alkaloids. Concise syntheses of (+/-)-akuammicine and (+/-)-strychnine.	2001 Aug 22	11506556
Centrally administered corticotropin-releasing hormone and peripheral injections of strychnine hydrochloride potentiate the acoustic startle response in preweanling rats.	2001 Dec	11770058
GABAergic and glycinergic neural inhibition in excitatory frequency tuning of bat inferior collicular neurons.	2001 Dec	11715077
Design of semicarbazones and their bio-isosteric analogues as potential anticonvulsants.	2001 Feb	11234338
The effect of proteolytic enzymes on the alpha9-nicotinic receptor-mediated response in isolated frog vestibular hair cells.	2001 Feb	11223279
A nonsense mutation in the alpha1 subunit of the inhibitory glycine receptor associated with bovine myoclonus.	2001 Feb	11178872
Electrophysiologic evidence for increased endogenous gabaergic but not glycinergic inhibitory tone in the rat spinal nerve ligation model of neuropathy.	2001 Feb	11176099
Swim stress alters the behavioural response of mice to GABA-related and some GABA-unrelated convulsants.	2001 Feb	11164703
Evidence of a functional alpha7-neuronal nicotinic receptor subtype located on motoneurons of the dorsal motor nucleus of the vagus.	2001 Feb	11160606
Mu opiates inhibit long-term potentiation induction in the spinal cord slice.	2001 Feb	11160487
Hamster sperm glycine receptor: evidence for its presence and involvement in the acrosome reaction.	2001 Feb	11139233
Acetylcholine-evoked calcium increases in Deiters' cells of the guinea pig cochlea suggest alpha9-like receptors.	2001 Feb 1	11170174
Spectral integration in the inferior colliculus: role of glycinergic inhibition in response facilitation.	2001 Feb 1	11157095
Non-enzymatic reduction of aliphatic tertiary amine N-oxides mediated by the haem moiety of cytochrome P450.	2001 Jan	11334263
Strychnogucines A and B, two new antiplasmodial bisindole alkaloids from Strychnos icaja.	2001 Jan	11170658
Slow dorsal-ventral rhythm generator in the lamprey spinal cord.	2001 Jan	11152721
The generation of rhythmic activity in dissociated cultures of rat spinal cord.	2001 Jul	11553272
Transition from GABAergic to glycinergic synaptic transmission in newly formed spinal networks.	2001 Jul	11431527
A critical role of the strychnine-sensitive glycinergic system in spontaneous retinal waves of the developing rabbit.	2001 Jul 15	11438591
Autoradiographic localization of [3H]thiocolchicoside binding sites in the rat brain and spinal cord.	2001 Jun	11406196
Strychnine, ammonia and gunpowder for snakebite--the end of an era.	2001 Jun 4	11453337
Glycine receptor mediated responses in rat histaminergic neurons.	2001 Mar 2	11172926
Effects of pituitary adenylate cyclase activating polypeptide on lumbosacral preganglionic neurons in the neonatal rat spinal cord.	2001 Mar 23	11259781
Ionotropic histamine receptors and H2 receptors modulate supraoptic oxytocin neuronal excitability and dye coupling.	2001 May 1	11312281
Role of protein kinase C in opioid modulation of glycine-gated Cl(-) current in rat periaqueductal gray neuron.	2001 Nov 16	11728420
Glycine receptor-mediated inhibition of dopamine and non-dopamine neurons of the rat ventral tegmental area in vitro.	2001 Nov 23	11701143
Are homeopathic studies better-fated in India?	2001 Oct	11760717
Subunit composition of strychnine-sensitive glycine receptors expressed by adult rat basolateral amygdala neurons.	2001 Oct	11683900
Characterization of the spontaneous synaptic activity of amacrine cells in the mouse retina.	2001 Oct	11600626
[Arsenic and strychnine against tired eyes].	2001 Oct 10	11699263
Electrophysiological evidence for vasopressin V(1) receptors on neonatal motoneurons, premotor and other ventral horn neurons.	2001 Sep	11535670
The release of spinal prostaglandin E2 and the effect of nitric oxide synthetase inhibition during strychnine-induced allodynia.	2001 Sep	11524348
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
Synchronization of an embryonic network of identified spinal interneurons solely by electrical coupling.	2001 Sep 27	11580902
Glycine receptors involved in synaptic transmission are selectively regulated by the cytoskeleton in mouse spinal neurons.	2002 Jan	11784780

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 GLYCEROPHOSPHATE

Common Name

English

STRYCHNINE, GLYCEROPHOSPHATE (2:1)

Common Name

English

STRYCHNINE COMPOUND WITH GLYCEROL PHOSPHATE (2:1)

Common Name

English

STRYCHNIDIN-10-ONE, COMPD. WITH 1,2,3-PROPANETRIOL MONO(DIHYDROGEN PHOSPHATE) (2:1)

Common Name

English

Strychnine glycerophosphate [WHO-DD]

Common Name

English

Code System Code Type Description

FDA UNII

C42CE367BZ