SELFOTEL

Details

Stereochemistry	RACEMIC
Molecular Formula	C7H14NO5P
Molecular Weight	223.1635
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)[C@@H]1C[C@H](CP(O)(O)=O)CCN1

InChI

InChIKey=LPMRCCNDNGONCD-RITPCOANSA-N

InChI=1S/C7H14NO5P/c9-7(10)6-3-5(1-2-8-6)4-14(11,12)13/h5-6,8H,1-4H2,(H,9,10)(H2,11,12,13)/t5-,6+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2899170 | https://www.ncbi.nlm.nih.gov/pubmed/23766625 | https://www.ncbi.nlm.nih.gov/pubmed/2850065 | https://www.ncbi.nlm.nih.gov/pubmed/2547931 | https://www.ncbi.nlm.nih.gov/pubmed/10657404 | https://www.ncbi.nlm.nih.gov/pubmed/10541229https://www.ncbi.nlm.nih.gov/pubmed/2899170

(+)-selfotel ((+)-CGS-19755) is an enantiomer of selfotel, a competitive antagonist at N-methyl-D-aspartate (NMDA)-preferring receptors. The inhibition of NMDA-evoked ACh release from rat striatal slices is stereospecific, with the (+)-enantiomer less potent than the (-)-enantiomer.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate NMDA receptor 46 Target ID: CHEMBL1907608 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2899170 \| https://www.ncbi.nlm.nih.gov/pubmed/2850065	Antagonist 2778		50.0 nM [IC50]
Glutamate NMDA receptor 46 Target ID: CHEMBL1907608 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2899170	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Head injury 5 Sources: http://adisinsight.springer.com/drugs/800001276 https://www.ncbi.nlm.nih.gov/pubmed/10541229 https://www.ncbi.nlm.nih.gov/pubmed/23766625	Primary	Phase III 656	Unknown Approved Use Unknown
Stroke 144 Sources: http://adisinsight.springer.com/drugs/800001276 https://www.ncbi.nlm.nih.gov/pubmed/10657404 https://www.ncbi.nlm.nih.gov/pubmed/23766625	Primary	Phase III 656	Unknown Approved Use Unknown
Unknown 2578

C_max

Value	Dose	Co-administered	Analyte	Population
20676 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7709405	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		SELFOTEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
31622 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7709405	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		SELFOTEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7709405	2 mg/kg single, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		SELFOTEL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 mg/kg single, intravenous Highest studied dose Dose: 2 mg/kg Route: intravenous Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: stroke Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	Other AEs: Agitation, Confusion... Other AEs: Agitation (66.7%) Confusion (50%) Delirium (33.3%) Paranoid reaction (50%) Coordination abnormal (16.7%) Aphasia (16.7%) Hallucination (50%) Sources: https://pubmed.ncbi.nlm.nih.gov/7709405

AEs

AE	Significance	Dose	Population
Aphasia	16.7%	2 mg/kg single, intravenous Highest studied dose Dose: 2 mg/kg Route: intravenous Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: stroke Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/7709405
Coordination abnormal	16.7%	2 mg/kg single, intravenous Highest studied dose Dose: 2 mg/kg Route: intravenous Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: stroke Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/7709405
Delirium	33.3%	2 mg/kg single, intravenous Highest studied dose Dose: 2 mg/kg Route: intravenous Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: stroke Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/7709405
Confusion	50%	2 mg/kg single, intravenous Highest studied dose Dose: 2 mg/kg Route: intravenous Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: stroke Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/7709405
Hallucination	50%	2 mg/kg single, intravenous Highest studied dose Dose: 2 mg/kg Route: intravenous Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: stroke Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/7709405
Paranoid reaction	50%	2 mg/kg single, intravenous Highest studied dose Dose: 2 mg/kg Route: intravenous Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: stroke Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/7709405
Agitation	66.7%	2 mg/kg single, intravenous Highest studied dose Dose: 2 mg/kg Route: intravenous Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/7709405	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: stroke Age Group: ADULT Sex: M Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/7709405

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 60	P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144204496	no
CYP3A4 1925	inducer 1573 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144204496	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144204496	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=144204496

PubMed

Title	Date	PubMed
CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist.	1988 Jul	2899170
Glutamatergic antagonism: effects on lidocaine-induced seizures in the rat.	1994 Oct	7943778
Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine.	1999 May	10215643
The 26th Congress of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine, Tromso, Norway, 13-17 June 2001.	2001 Aug	11511333
A comparative assessment of the efficacy and side-effect liability of neuroprotective compounds in experimental stroke.	2001 Feb 23	11172782
Regional distribution and pharmacological characteristics of [3H]N-acetyl-aspartyl-glutamate (NAAG) binding sites in rat brain.	2001 Jan	10913688
Effects of antagonism of NMDA receptors on transient lower esophageal sphincter relaxations in the dog.	2001 Nov 16	11728433
Glutamate AMPA receptor antagonist treatment for ischaemic stroke.	2002	12365832
Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity.	2002	12192617
Stroke: trial by jury.	2003	12584420
Glutamate receptor antagonists modulate heat shock protein response in focal brain ischemia.	2003 Mar	12635523
Lessons from epidemiologic studies in clinical trials of traumatic brain injury.	2004	15335108
Nicotine exerts a permissive role on NMDA receptor function in hippocampal noradrenergic terminals.	2004 Jul	15165834
The rise and fall of NMDA antagonists for ischemic stroke.	2004 Mar	15032709
Neuroprotection against ischemic/hypoxic brain damage: blockers of ionotropic glutamate receptor and voltage sensitive calcium channels.	2004 Oct	15473250
Acute nociceptive somatic stimulus sensitizes neurones in the spinal cord to colonic distension in the rat.	2004 Oct 1	15284340
Cerebral perfusion pressure and risk of brain hypoxia in severe head injury: a prospective observational study.	2005	16356218
Cognitive effects of dopaminergic and glutamatergic blockade in nucleus accumbens in pigeons.	2005 Aug	15979133
Homocysteine, a risk factor for atherosclerosis, biphasically changes the endothelial production of kynurenic acid.	2005 Jul 11	15961072
Effects of the N-methyl-D-aspartate receptor antagonist perzinfotel [EAA-090; [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)-ethyl]phosphonic acid] on chemically induced thermal hypersensitivity.	2005 Jun	15764736
The NMDA receptor complex: a long and winding road to therapeutics.	2005 Mar	15772895
Methodological quality of animal studies on neuroprotection in focal cerebral ischaemia.	2005 Sep	16170651
Severe brain injury ICU outcomes are associated with Cranial-Arterial Pressure Index and noninvasive Bispectral Index and transcranial oxygen saturation: a prospective, preliminary study.	2006	17105656
Glutamate receptors in neuroinflammatory demyelinating disease.	2006	16883070
The NMDA receptor antagonist CGS 19755 disrupts recovery following cerebellar lesions.	2006	16518022
Some prognostic models for traumatic brain injury were not valid.	2006 Feb	16426948
Neuroprotection associated with alternative splicing of NMDA receptors in rat cortical neurons.	2006 Mar	16314856
NMDA receptor activity in learning spatial procedural strategies II. The influence of cerebellar lesions.	2006 Oct 16	17027771
NMDA receptor activity in learning spatial procedural strategies I. The influence of hippocampal lesions.	2006 Oct 16	17027770
Acute D2/D3 dopaminergic agonism but chronic D2/D3 antagonism prevents NMDA antagonist neurotoxicity.	2006 Sep 15	16616728
Intracranial pressure monitoring in intensive care: clinical advantages of a computerized system over manual recording.	2007	17233895
Increased cerebral oxygen consumption in Eker rats and effects of N-methyl-D-aspartate blockade: Implications for autism.	2007 Aug 15	17549750
Repeated treatment with N-methyl-d-aspartate antagonists in neonatal, but not adult, rats causes long-term deficits of radial-arm maze learning.	2007 Sep 12	17706184
Risks associated with magnetic resonance imaging and cervical collar in comatose, blunt trauma patients with negative comprehensive cervical spine computed tomography and no apparent spinal deficit.	2008	18625041
Pharmacology of traumatic brain injury: where is the "golden bullet"?	2008 Nov-Dec	18769636
Molecular mechanisms of traumatic brain injury: the missing link in management.	2009 Feb 2	19187555
NMDA-mediated modulation of dopamine release is modified in rat prefrontal cortex and nucleus accumbens after chronic nicotine treatment.	2009 Jan	19046354
Cerebral vasospasm following traumatic subarachnoid hemorrhage.	2009 Nov	21772907
Resistin is associated with mortality in patients with traumatic brain injury.	2010	21029428
Integrative emphases on intimate, intrinsic propensity/pathological processes--causes of self recovery limits and also, subtle related targets for neuroprotectionl pleiotropicity/multimodal actions, by accessible therapeutic approaches--in spinal cord injuries.	2010 Jul-Sep	20945817

Patents

Sample Use Guides

In Vivo Use Guide

Two pivotal phase 3 ischemic stroke trials tested the hypothesis, by double-blind, randomized, placebo-controlled parallel design, that a single intravenous 1.5 mg/kg dose of Selfotel, administered within 6 hours of stroke onset, would improve functional outcome at 90 days, defined as the proportion of patients achieving a Barthel Index score of >/=60. The trials were performed in patients aged 40 to 85 years with acute ischemic hemispheric stroke and a motor deficit.

Route of Administration: Intravenous

In Vitro Use Guide

Selfotel (CGS 19755 [cis-4-phosphonomethyl-2-piperidine carboxylic acid]) was found to be a potent, stereospecific inhibitor of N-methyl-D-aspartate (NMDA)-evoked, but not KCl-evoked, [3H] acetylcholine release from slices of the rat striatum. The concentration-response curve to NMDA was shifted to the right by CGS 19755 (pA2 = 5.94), suggesting a competitive interaction with NMDA-type receptors.

Name

Type

Language

SELFOTEL

Official Name

English

SELFOTEL [USAN]

Common Name

English

CPDD-0027

Code

English

Selfotel [WHO-DD]

Common Name

English

CGS-19755

Code

English

SELFOTEL [MART.]

Common Name

English

CIS-4-(PHOSPHONOMETHYL)-2-PIPERIDINE CARBOXYLIC ACID

Systematic Name

English

2-PIPERIDINECARBOXYLIC ACID, 4-(PHOSPHONOMETHYL)-, CIS-

Common Name

English

CGS 19755

Code

English

selfotel [INN]

Common Name

English

GNF-PF-157

Code

English

2-PIPERIDINECARBOXYLIC ACID, 4-(PHOSPHONOMETHYL)-, (2R,4S)-REL-

Systematic Name

English

Classification Tree Code System Code

WIKIPEDIA

NMDA receptor antagonist