Deleted member 170540
Bluelight Crew
The cholinergic M5 receptor is the most recently found acetylcholine receptor, and these receptors are found in high concentration in the nucleus accumbens, where their activation promotes, and is necessary for, the release of dopamine.
M5 knockout mice get less easily addicted to cocaine or opioids because the lack of M5 receptors prevents prolonged dopaminergic effect caused by these drugs. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2009.01059.x/pdf
M3 receptors have the opposite function, and agonist binding to them causes reduced dopamine release. In fact the potent M3 agonist oxotremorine causes parkinsonian-like symptoms due to this effect.
One selective M5 agonist is the experimental compound VU-0238429 (see image)
Could this or some other selective M5 agonist/allosteric modulator be 'recreational'? They should increase dopamine release in the 'pleasure circuitry' of the brain... Also, does the mild mood-elevating effect of scopolamine and other anticholinergics result from the blockage of M3 receptors?
Unselective muscarine agonists can't be used for this purpose, as the activation of the other M receptor subtypes causes unpleasant peripheral symptoms, like increased sweating and lacrimation, bradycardia and urinary incontinence.
M5 knockout mice get less easily addicted to cocaine or opioids because the lack of M5 receptors prevents prolonged dopaminergic effect caused by these drugs. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2009.01059.x/pdf
M3 receptors have the opposite function, and agonist binding to them causes reduced dopamine release. In fact the potent M3 agonist oxotremorine causes parkinsonian-like symptoms due to this effect.
One selective M5 agonist is the experimental compound VU-0238429 (see image)
Could this or some other selective M5 agonist/allosteric modulator be 'recreational'? They should increase dopamine release in the 'pleasure circuitry' of the brain... Also, does the mild mood-elevating effect of scopolamine and other anticholinergics result from the blockage of M3 receptors?
Unselective muscarine agonists can't be used for this purpose, as the activation of the other M receptor subtypes causes unpleasant peripheral symptoms, like increased sweating and lacrimation, bradycardia and urinary incontinence.
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