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upregulate muscarinic acetylcholine


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#1 metabrain

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Posted 23 November 2018 - 12:18 PM

Is it possible to upregulate muscarinic acetylcholine on a permanent basis i.e. the receptors will be denser or more activated even after the substance upregulating them is removed?

#2 MankindRising

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Posted 23 November 2018 - 04:24 PM

Some of the well known herbal supps/noots do this:


* piracetam (study didnt say which subtypes get upregulated)

* ginkgo (m1 muscarainic)

* alpha lipoic acid (m1 and m2)

* probably lots more but those 3 are the ones that came to mind.

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#3 CWF1986

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Posted 26 November 2018 - 11:45 PM

Do keep in mind that upregulating Machr is not beneficial for everyone.  For some it does everything that the noot sites tell you like increased energy, focus, and concentration.  For me, anything with the exception of racetams that's M-cholinergic is extreme anxiety, IBS type symptoms, and despair in a pill/powder.  


There's a few threads/posters that suggest that there might be a sort of spectrum ranging from low dopamine, high ach to high dopamine, low ach.  They work in sort of a seesaw pattern.  In fact, old school parkinson's meds were very powerful anti-cholinergics as a way of increasing dopamine and this would reduce the shaking.  There's even a theory that depression can be caused by an cholinergic/adrenergic imbalance.  


I'm not saying it's a bad idea, but I would find out how I respond to the regular more vanilla cholinergics before looking into more permanent ways of doing this.  This is a process that I can't imagine taking less than months.


Regardless of your choice, I hope it works out well for you.  

#4 Pereise1

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Posted 30 November 2018 - 05:17 PM

From examine.com, Magnolia Bark Extract upregulates muscarinic receptors:


The neolignans (magnolol and honokiol) appear to increase the affinity of muscarine to its receptor (the muscarinic acetylcholine receptors) due to allosterically modifying low affinity receptors to a higher binding capacity, thus causing a greater amount of overall binding.[25] Honokiol and magnolol were both effective, and increased binding 3.2-fold and 2.8-fold (respectively) in rat forebrains and 71% and 64% (respectively) in the cerebellum.[25]



Curcumin activates M1 receptors, not too sure if it upregulates it at all (https://www.ncbi.nlm...pubmed/19765405)


Berberine activates M2 receptors (https://www.ncbi.nlm...pubmed/21168503)


Some antipsychotics upregulates muscarinic receptors:


Effects of antipsychotic medication on muscarinic M1 receptor mRNA expression in the rat brain.

Alterations in muscarinic M1 receptor protein and mRNA expression have been revealed in post-mortem brains of schizophrenia patients. Most patients had been treated with antipsychotics, so medication effects cannot be excluded as a possible explanation for these results. With in situ hybridization, this study investigated M1 receptor mRNA expression in rats treated with the typical antipsychotic haloperidol (0.3 mg/kg/day) and the atypical antipsychotics olanzapine (1.5 mg/kg/day) and aripiprazole (2.25 mg/kg/day) for 1 or 12 weeks. Compared with the control group, haloperidol significantly increased (approximately 13-21%, P < 0.05) M1 mRNA expression in the CA1, CA2, and CA3 regions of the hippocampus after both 1 and 12 weeks of treatment, and it also increased (approximately 17%, P < 0.01) M1 mRNA expression in the substantia nigra compacta after 1 week of treatment. Olanzapine significantly increased (14-22%, P < 0.05) M1 mRNA expression in the hippocampus (CA1, CA2, and CA3) and substantia nigra compacta after 12 weeks of treatment, but not after 1 week. Aripiprazole significantly increased (17%, P < 0.01) M1 mRNA expression in the hippocampus (CA1) after both 1 and 12 week treatments and increased (12%, P < 0.05) M1 mRNA expression in the nucleus accumbens after 1 week of treatment. Despite their different affinities for muscarinic M1 receptors, all three antipsychotic medications induced a similar trend of change in M1 mRNA expression in selected brain regions. These data suggest that the decreased M1 receptor protein and mRNA expression observed in schizophrenia patients is unlikely to be a consequence of drug treatments and implicates muscarinic M1 receptors in the pharmacotherapy of the disease.


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#5 Pereise1

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Posted 17 December 2018 - 06:25 PM

Here's a few more:



BDNF through Trkb receptors:

We found that blocking the trkB signaling cascade affects the functional expression of the presynaptic mAChR release-modulatory pathways. The M1 release-potentiating pathway (Fig. 7, point 1) (Santafé et al., 20032006) does not operate (it lacks a hypothesized point 3 that enables the M1 mechanism), whereas the M2inhibitory mechanism (point 4) (Santafé et al., 20032006) reverses its normal coupling to transmitter release after trkB block, resulting in a clear potentiating effect (point 8). The lack of a hypothesized point 6 that enables the normal M2 inhibitory mechanism may unmask an M2-mediated potentiation. In previous studies, we found similar changes in the M2-mediated mAChR function (reversion) (Santafé et al., 20062007) in several conditions, all of which have either low ACh release or low ACh in the synaptic cleft: (1) developing synapses in newborn animals, (2) protein kinase A block with H-89, (3) high external magnesium, (4) low external calcium, and (5) increased acetylcholinesterase in the synaptic cleft. Thus, the low release produced by interference with the trkB receptor (point 7) may be the cause of the functional anomaly in the muscarinic pathway. However, in the five situations mentioned above, both M1 and M2 mAChRs stimulate ACh release, whereas M1 does not work in the trkB blocked preparation. Interestingly, then, K-252a-induced trkB block is the only one of many conditions that inactivates the ACh release-enhancing M1 function. This clearly indicates that the trkB normal function modulates both M1 and M2muscarinic pathways.





Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain.

1. Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors. 2. The density of cortical A1 adenosine receptors is increased by 20%, while the density of striatal A2A adenosine receptors is unaltered. 3. The densities of cortical beta 1 and cerebellar beta 2 adrenergic receptors are reduced by ca. 25%, while the densities of cortical alpha 1 and alpha 2 adrenergic receptors are not significantly altered. Densities of striatal D1 and D2 dopaminergic receptors are unaltered. The densities of cortical 5 HT1 and 5 HT2 serotonergic receptors are increased by 26-30%. Densities of cortical muscarinic and nicotinic receptors are increased by 40-50%. The density of cortical benzodiazepine-binding sites associated with GABAA receptors is increased by 65%, and the affinity appears slightly decreased. The density of cortical MK-801 sites associated with NMDA-glutaminergic receptors appear unaltered. 4. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%. 5. The results indicate that chronic ingestion of caffeine equivalent to about 100 mg/kg/day in mice causes a wide range of biochemical alterations in the central nervous system.




CDP-Choline (from examine.com):

In the striatum and cortex the protein content of the vesicular acetylcholine transporter appears to be increased with supplemental CDP-Choline (325mg/kg), which also appears to apply to Alpha-GPC when controlled for choline content (although alpha-GPC affected more brain regions overall).[68][69] This has been noted in a living system, where aged rats given 100-500mg/kg CDP-Choline daily for 7 months experienced a 6-17% increase in muscarinic acetylcholine receptor concentration (whereas control experienced a decline) although affinity of the receptor was not modified.[70]




Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and muscarinic receptors induced by cycloheximide.

The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)-acetamide [DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre- and post-training and pre-retention test administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. Aniracetam, another cyclic derivative of GABA, also showed antiamnesic effects. Scopolamine, a muscarinic ACh receptor antagonist, and the GABA antagonists, picrotoxin and bicuculline, all antagonized the antiamnesic effects of DM-9384. CXM decreased the number of GABAA and muscarinic ACh receptor binding sites. DM-9384 not only inhibited this effect but actually increased the latter. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with GA-BAergic and AChergic neuronal systems and enhancing protein synthesis in the brain.


And Galantamine (M1):


Galantamine promotes adult hippocampal neurogenesis via M₁ muscarinic and α7 nicotinic receptors in mice.

Galantamine, an inhibitor of acetylcholinesterase, promotes hippocampal neurogenesis, but the exact mechanism for this is not known. In the present study, we examined the mechanisms underlying the effects of acute galantamine on neurogenesis in the mouse hippocampus. Galantamine (3 mg/kg) increased the number of 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the subgranular zone of the dentate gyrus. This effect was blocked by the muscarinic receptor antagonist scopolamine and the preferential M1 muscarinic receptor antagonist telenzepine, but not by the nicotinic receptor antagonists mecamylamine and methyllycaconitine. Galantamine did not alter the ratio of neuronal nuclei (NeuN)- or glial fibrillary acidic protein (GFAP)-positive cells to BrdU-labeled cells in the subgranular zone and granule cell layer. Galantamine (1, 3 mg/kg) promoted the survival of 2-wk-old newly divided cells in mice in the granule cell layer of the dentate gyrus, whereas it did not affect the survival of newly divided cells at 1 and 4 wk. Galantamine-induced increases in cell survival were blocked by the α7 nicotinic receptor antagonist methyllycaconitine, but not by scopolamine. Bilateral injection of recombinant IGF2 into the dentate gyrus of the hippocampus mimicked the effects of galantamine. The effects of galantamine were blocked by direct injection of the IGF1 receptor antagonist JB1. These findings suggest that galantamine promotes neurogenesis via activation of the M1 muscarinic and α7 nicotinic acetylcholine receptors. The present study also suggests that IGF2 is involved in the effects of galantamine on the survival of 2-wk-old immature cells in the granule cell layer.




Edited by Pereise1, 17 December 2018 - 06:49 PM.

Also tagged with one or more of these keywords: acetylcholine

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