DEXANABINOL

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H38O3
Molecular Weight	386.5674
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CC(CO)=CC[C@]1([H])C(C)(C)OC3=C2C(O)=CC(=C3)C(C)(C)CCCCCC

InChI

InChIKey=SSQJFGMEZBFMNV-PMACEKPBSA-N

InChI=1S/C25H38O3/c1-6-7-8-9-12-24(2,3)18-14-21(27)23-19-13-17(16-26)10-11-20(19)25(4,5)28-22(23)15-18/h10,14-15,19-20,26-27H,6-9,11-13,16H2,1-5H3/t19-,20-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=720043 | DOI: 10.1002/1098-2299(200007/08)50:3/4<211::AID-DDR3>3.0.CO;2-G | https://www.ncbi.nlm.nih.gov/pubmed/16361021 | https://www.ncbi.nlm.nih.gov/pubmed/14534855

Dexanabinol is the synthetic cannabinoid. It is inactive as a cannabimimetic, but exhibits pharmacological properties characteristic of an N-methyl-D-aspartate (NMDA)-receptor antagonist. It blocks NMDA-receptors stereospecifically by interacting with a site close to, but distinct from, that of uncompetitive NMDA-receptor antagonists and from the recognition sites of glutamate, glycine, and polyamines. This agent also scavenges peroxy radicals and protects neurons from the damages of reactive oxygen species. Furthermore, dexanabinol inhibits the activity of nuclear factor kappa B (NF-kB), thereby preventing the expression of NF-kB target genes, such as tumor necrosis factor alpha, cytokines and inducible nitric oxide synthase. Dexanabinol is a potent cerebroprotective agent, with a therapeutic window of about 4 h. Dexanabinol is safe, but is not efficacious in the treatment of traumatic brain injury. It was introduced into clinical trials for breast cancer and advanced solid tumors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glutamate [NMDA] receptor 125 Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9424014 \| DOI: 10.1002/1098-2299(200007/08)50:3/4<211::AID-DDR3>3.0.CO;2-G	Antagonist 2778
Oxidative Stress 160 Target ID: WP408 Sources: DOI: 10.1002/1098-2299(200007/08)50:3/4<211::AID-DDR3>3.0.CO;2-G	Inhibitor 8297
Nuclear factor NF-kappa-B complex 11 Target ID: CHEMBL2094258 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15380375 \| https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=720043	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Traumatic brain injury 9 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16361021	Primary	Phase III 656	Unknown Approved Use Unknown
Brain cancer 10 Sources: https://clinicaltrials.gov/ct2/show/NCT01654497 http://adisinsight.springer.com/drugs/800003708	Primary	Phase I 428	Unknown Approved Use Unknown
Advanced solid cancer 28 Sources: https://clinicaltrials.gov/ct2/show/NCT01489826 http://adisinsight.springer.com/drugs/800003708	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
4226 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	24 mg/kg 1 times / week multiple, intravenous dose: 24 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7018 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	28 mg/kg 1 times / week multiple, intravenous dose: 28 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
813 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	8 mg/kg 1 times / week multiple, intravenous dose: 8 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
20139 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	36 mg/kg 1 times / week multiple, intravenous dose: 36 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
204 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	2 mg/kg 1 times / week multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2885 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	16 mg/kg 1 times / week multiple, intravenous dose: 16 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
387 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	4 mg/kg 1 times / week multiple, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
10800 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	24 mg/kg 1 times / week multiple, intravenous dose: 24 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15400 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	28 mg/kg 1 times / week multiple, intravenous dose: 28 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1890 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	8 mg/kg 1 times / week multiple, intravenous dose: 8 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
38300 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	36 mg/kg 1 times / week multiple, intravenous dose: 36 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
475 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	2 mg/kg 1 times / week multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5750 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	16 mg/kg 1 times / week multiple, intravenous dose: 16 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
881 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	4 mg/kg 1 times / week multiple, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
3.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	24 mg/kg 1 times / week multiple, intravenous dose: 24 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	28 mg/kg 1 times / week multiple, intravenous dose: 28 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	8 mg/kg 1 times / week multiple, intravenous dose: 8 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	36 mg/kg 1 times / week multiple, intravenous dose: 36 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	2 mg/kg 1 times / week multiple, intravenous dose: 2 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	16 mg/kg 1 times / week multiple, intravenous dose: 16 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33615223	4 mg/kg 1 times / week multiple, intravenous dose: 4 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:	DEXANABINOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34400	https://www.001chemical.com/chem/search?q=DY34400
AK Scientific	1714AH	https://aksci.com/item_detail.php?cat=1714AH
ApexBio Technology	B5343	https://www.apexbt.com/catalogsearch/result/?q=B5343
Cayman Chemical	10006350	http://www.caymanchem.com/app/template/Product.vm/catalog/10006350
Chem Scene	CS-0025698	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0025698
Molcore	MC34400	http://www.molcore.com/CatMC34400.html
MuseChem	R060139	https://www.musechem.com/product/R060139.html
Tetrahedron	TS80585	http://www.thsci.com/search.do?q=TS80585
Tocris	2861	https://www.tocris.com/search.php?Type=QuickSearch&Value=2861
Toronto Research Chemicals	KIT4870	https://www.trc-canada.com/product-detail/?CatNum=KIT4870

PubMed

Title	Date	PubMed
Cardiovascular effects of (-)-11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl in rats.	1996 Aug	8856492
Cannabinoid-induced hypotension and bradycardia in rats mediated by CB1-like cannabinoid receptors.	1997 Jun	9190833
Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid.	1997 Nov	9353414
Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors.	1999 Nov 23	10570211
CB1 cannabinoid receptor-mediated cell migration.	2000 Jul	10871313
Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation.	2000 Mar	10700234
Involvement of central and peripheral cannabinoid receptors in the regulation of heart resistance to arrhythmogenic effects of epinephrine.	2000 Nov	11182823
[Antiarrhythmic properties of a cannabinoid (CB) receptor agonist].	2001 May-Jun	11558437
A cannabinoid mechanism in relapse to cocaine seeking.	2001 Oct	11590440
Cannabinoid activity curtails cocaine craving.	2001 Oct	11590424
CB1 cannabinoid receptor-mediated tyrosine phosphorylation of focal adhesion kinase-related non-kinase.	2002 Aug 14	12163181
Cannabinoid agonists attenuate capsaicin-induced responses in human skin.	2003 Apr	12670670
Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with lypopolysaccharide.	2003 Jan 15	12509806
Cannabinoid receptor activation in the rostral ventrolateral medulla oblongata evokes cardiorespiratory effects in anaesthetised rats.	2003 Sep	12970095
The endogenous cannabinoid system protects against colonic inflammation.	2004 Apr	15085199
Corticotropin-releasing hormone (CRH) mRNA expression in rat central amygdala in cannabinoid tolerance and withdrawal: evidence for an allostatic shift?	2004 Jan	12968131
The cannabinoid dexanabinol is an inhibitor of the nuclear factor-kappa B (NF-kappa B).	2004 Sep	15380375
Cocaine- and amphetamine-related transcript is involved in the orexigenic effect of endogenous anandamide.	2005	16131814
CB(1) cannabinoid receptor stimulation modulates transient receptor potential vanilloid receptor 1 activities in calcium influx and substance P Release in cultured rat dorsal root ganglion cells.	2005 Mar	15750287
The G alpha(o/i)-coupled cannabinoid receptor-mediated neurite outgrowth involves Rap regulation of Src and Stat3.	2005 Sep 30	16046413
F200A substitution in the third transmembrane helix of human cannabinoid CB1 receptor converts AM2233 from receptor agonist to inverse agonist.	2006 Feb 15	16438957
Cannabinoids ameliorate pain and reduce disease pathology in cerulein-induced acute pancreatitis.	2007 May	17484889
Agonist selective modulation of tyrosine hydroxylase expression by cannabinoid ligands in a murine neuroblastoma cell line.	2007 Sep	17540007
ERK signalling pathway is not involved in PSA-NCAM-dependent alterations of hippocampal plasticity evoked by CB1 receptor activation.	2009 Nov-Dec	20081235
The effects of cannabinoid drugs on abnormal involuntary movements in dyskinetic and non-dyskinetic 6-hydroxydopamine lesioned rats.	2010 Dec 2	20888328
Brain-derived neurotrophic factor controls cannabinoid CB1 receptor function in the striatum.	2010 Jun 16	20554863
Behavioural and molecular consequences of chronic cannabinoid treatment in Huntington's disease transgenic mice.	2010 Sep 29	20600638
Effects of cannabinoids and related fatty acids upon the viability of P19 embryonal carcinoma cells.	2013 Nov	23552853
Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death.	2014 Jan 1	24211273

Patents

Sample Use Guides

In Vivo Use Guide

Single injection of 150 mg dexanabinol, given within 6 h of injury

Route of Administration: Intravenous

In Vitro Use Guide

Dexanabinol inhibited the binding of the radioactive dopamine D1 receptor antagonist only at a very high concentration: 50 uM Dexanabinol inhibited 29.7 % of the specific binding of [3H]SCH-23390 to the forebrain membranes, while 100 uM inhibited 52.7%.

Name

Type

Language

DEXANABINOL

Common Name

English

Sinnabidol [WHO-DD]

Common Name

English

SINNABIDOL

Common Name

English

(6AS,10AS)-9-(HYDROXYMETHYL)-6,6-DIMETHYL-3-(2-METHYLOCTAN-2-YL)- 6A,7,10,10A-TETRAHYDROBENZO(C)CHROMEN-1-OL

Common Name

English

DEXANABINOL [MI]

Common Name

English

PRS-211007-000

Code

English

11-OH-THC

Common Name

English

(+)-HU-210

Code

English

6H-DIBENZO(B,D)PYRAN-9-METHANOL, 3-(1,1-DIMETHYLHEPTYL)-6A,7,10,10A-TETRAHYDRO-1-HYDROXY-6,6-DIMETHYL-, (6AS,10AS)-

Systematic Name

English

HU-211

Code

English

PA-50211

Code

English

PRS-211007

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

179803