| Candidate ID: | R1514 |
| Source ID: | DB14011 |
| Source Type: | investigational |
| Compound Type: |
small molecule
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| Compound Name: |
Nabiximols
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| Synonyms: |
Nabiximols
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| Molecular Formula: |
C42H60O4
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| SMILES: |
[H][C@]1(CCC(C)=C[C@@]1([H])C1=C(O)C=C(CCCCC)C=C1O)C(C)=C.[H][C@@]12CCC(C)=C[C@@]1([H])C1=C(O)C=C(CCCCC)C=C1OC2(C)C
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| Structure: |
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| DrugBank Description: |
Nabiximols (tradename Sativex®) is a whole plant extract from the Cannabis species _Cannabis sativa L._ that has been purified into the active components CBD (cannabidiol) and THC (delta-9-tetrahydrocannabinol). For trademark purposes, purified CBD is branded as Nabidiolex®, while THC is purified as the product Tetrabinex®. Sativex® is available in a 1:1 formulation of THC:CBD as an oro-mucosal pump spray used for treatment of neuropathic pain from Multiple Sclerosis (MS) and for intractable cancer pain. Although still largely debated, Cannabis has been shown to have analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant, and anti-psychotic activity .
From a pharmacological perspective, Cannabis' diverse receptor profile explains its potential application for such a wide variety of medical conditions. Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon cannabinoid receptors of the body . Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two types of cannabinoids found naturally in the resin of the marijuana plant, both of which interact with the cannabinoid receptors found in the human body. While both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. While cannabis in its natural plant form is currently used "off-label" for the management of many medical conditions, THC is currently commercially available in synthetic form as , as purified isomer as , or in a 1:1 formulation with CBD from purified plant extract as .
The primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects .
In Canada, Sativex® has received a Notice of Compliance (NOC) for use as an as adjunctive treatment for symptomatic relief of spasticity in patients with multiple sclerosis (MS) who have not responded adequately to other therapy and who demonstrate meaningful improvement during an initial trial of therapy.
Sativex® has also received a Notice of Compliance with Conditions (NOC/c) for use as an adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis (MS) and as adjunctive analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain during the highest tolerated dose of strong opioid therapy for persistent background pain.
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| CAS Number: |
56575-23-6
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| Molecular Weight: |
628.938
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| DrugBank Indication: |
In Canada, Sativex has received a Notice of Compliance (NOC) for use as an as adjunctive treatment for symptomatic relief of spasticity in patients with multiple sclerosis (MS) who have not responded adequately to other therapy and who demonstrate meaningful improvement during an initial trial of therapy.
Sativex has also received a Notice of Compliance with Conditions (NOC/c) for use as an adjunctive treatment for the symptomatic relief of neuropathic pain in adult patients with multiple sclerosis (MS) and as adjunctive analgesic treatment in adult patients with advanced cancer who experience moderate to severe pain during the highest tolerated dose of strong opioid therapy for persistent background pain.
Marketing authorisations with conditions reflect the promising nature of the clinical evidence and the need for confirmatory studies to verify the clinical benefit. Patients should be advised of the conditional nature of the authorizations with conditions.
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| DrugBank Pharmacology: |
The principal pharmacological effects of THC include analgesic, muscle relaxant, antiemetic, appetite stimulant and psychoactive effects. CBD has analgesic, anticonvulsant, muscle relaxant, anxiolytic, neuroprotective, anti-oxidant and anti-psychotic activity.
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| DrugBank MoA: |
The primary psychoactive component of Cannabis, delta 9-tetrahydrocannabinol (Δ9-THC), demonstrates its effects through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors. This activity results in the well-known effects of smoking cannabis such as increased appetite, reduced pain, and changes in emotional and cognitive processes. In contrast to THC's weak agonist activity, CBD has been shown to act as a negative allosteric modulator of the cannabinoid CB1 receptor, the most abundant G-Protein Coupled Receptor (GPCR) in the body . Allosteric regulation is achieved through the modulation of receptor activity on a functionally distinct site from the agonist or antagonist binding site. The negative allosteric modulatory effects of CBD are therapeutically important as direct agonists are limited by their psychomimetic effects while direct antagonists are limited by their depressant effects .
There is further evidence that CBD also activates 5-HT1A serotonergic and TRPV1–2 vanilloid receptors, antagonizes alpha-1 adrenergic and µ-opioid receptors, inhibits synaptosomal uptake of noradrenaline, dopamine, serotonin and gaminobutyric acid and cellular uptake of anandamide, acts on mitochondria Ca2 stores, blocks low-voltage-activated (T-type) Ca2 channels, stimulates activity of the inhibitory glycine-receptor, and inhibits activity of fatty amide hydrolase (FAAH) .
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| Targets: |
Cannabinoid receptor 1; Cannabinoid receptor 2; G-protein coupled receptor 12 inverse agonist; Glycine receptor subunit alpha-1; Glycine receptor (alpha-1/beta); Glycine receptor subunit alpha-3; N-arachidonyl glycine receptor; G-protein coupled receptor 55; 5-hydroxytryptamine receptor 1A; 5-hydroxytryptamine receptor 2A; Neuronal acetylcholine receptor subunit alpha-7; Delta-type opioid receptor; Mu-type opioid receptor; Peroxisome proliferator-activated receptor gamma; Transient receptor potential cation channel subfamily V member 1; Voltage-dependent T-type calcium channel subunit alpha-1G; Voltage-dependent T-type calcium channel subunit alpha-1H; Voltage-dependent T-type calcium channel subunit alpha-1I; Transient receptor potential cation channel subfamily A member 1; Transient receptor potential cation channel subfamily M member 8; Transient receptor potential cation channel subfamily V member 2; Transient receptor potential cation channel subfamily V member 3; Transient receptor potential cation channel subfamily V member 4; Voltage-dependent anion-selective channel protein 1; Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Acetyl-CoA acetyltransferase, mitochondrial inhibitor; Steroid 17-alpha-hydroxylase/17,20 lyase inhibitor; 3-hydroxy-3-methylglutaryl-coenzyme A reductase stimulator; Glutathione reductase, mitochondrial stimulator; Glutathione peroxidase 1 stimulator; Indoleamine 2,3-dioxygenase 1 inhibitor; Arylalkylamine N-acetyltransferase inhibitor; Cytochrome P450 1B1 inhibitor; Cytochrome P450 3A5 inhibitor; Cytochrome P450 2D6 substrate&inhibitor; Cytochrome P450 1A2 inhibitor; Cytochrome P450 1A1 inhibitor; Cytochrome P450 3A7 inhibitor; Quinone oxidoreductase inhibitor; Catalase inhibitor; Fatty-acid amide hydrolase 1 inhibitor&inducer; Superoxide dismutase [Cu-Zn] inhibitor; N-acylethanolamine-hydrolyzing acid amidase inhibitor
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| Inclusion Criteria: |
Target associated
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