WIN 55,212-2 is a chemical described as an

aminoalkylindole Aminoalkylindoles (AAIs) are a family of cannabinergic compound that act as a cannabinoid receptor agonist. They were invented by pharmaceutical company Sterling-Winthrop in the early 1990s as potential nonsteroidal anti-inflammatory agents. Leg ...

derivative, which produces effects similar to those of

cannabinoid Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

s such as

tetrahydrocannabinol Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC'' ...

(THC) but has an entirely different

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of at ...

. WIN 55,212-2 is a potent cannabinoid

receptor agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an ...

that has been found to be a potent analgesic in a rat model of neuropathic pain. It activates p42 and p44

MAP kinase A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses ...

via receptor-mediated signaling. At 5 μM WIN 55,212-2 inhibits ATP production in

sperm Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...

in a CB₁ receptor-dependent fashion. WIN 55,212-2, along with

HU-210 HU-210 is a synthetic cannabinoid that was first synthesized in 1988 from (1R,5S)-myrtenol by a group led by Raphael Mechoulam at the Hebrew University. HU-210 is 100 to 800 times more potent than natural THC from cannabis and has an extended d ...

and JWH-133, may prevent the inflammation caused by

amyloid beta Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...

proteins involved in

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

, in addition to preventing cognitive impairment and loss of neuronal markers. This anti-inflammatory action is induced through agonist action at

cannabinoid receptor Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid recepto ...

s, which prevents microglial activation that elicits the inflammation. WIN 55,212-2 is a full agonist at the CB₁ cannabinoid receptor ( ''K''_i = 1.9 nM) and has much higher affinity than

THC Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC' ...

(''K''_i = 41 nM) for this receptor. WIN 55,212-2 is also an agonist of the

PPARα Peroxisome proliferator-activated receptor alpha (PPAR-α), also known as NR1C1 (nuclear receptor subfamily 1, group C, member 1), is a nuclear receptor protein functioning as a transcription factor that in humans is encoded by the ''PPARA'' gen ...

and

PPARγ Peroxisome proliferator- activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a tran ...

nuclear receptors. WIN 55,212-2 reduces voluntary wheel running in laboratory mice, but with effects that depend on both genetic background and sex. In the United States, all CB₁ receptor agonists of the 3-(1-naphthoyl)indole class such as WIN 55,212-2 are

Schedule I Controlled Substance This is the list of Schedule I drugs as defined by the United States Controlled Substances Act. 21 CFRbr>1308.11(CSA Sched I) with changes through (Oct 18, 2012). Retrieved September 6, 2013. The following findings are required for drugs to be pl ...

s. WIN 55,212-2 is illegal in the UK.

References

External links

* {{Transient receptor potential channel modulators Aminoalkylindoles 4-Morpholinyl compunds Naphthoylindoles WIN compounds CB1 receptor agonists

See also

References

Further reading

External links