These compounds act on acetylcholine receptors. NewMind primarily stocks direct or indirect cholinergic agonists which are of interest to researchers involved in cognitive development studies, research into neurodegenerative diseases, and biochemical pathways of the parasympathetic nervous system.

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Centrophenoxine HCl, ≥98% Centrophenoxine HCl, ≥98%

Centrophenoxine HCl, ≥98%

Procholinergic with nootropic properties. Mild cerebral activator.

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GTS-21 HCl, ≥98% GTS-21 HCl, ≥98%

GTS-21 HCl, ≥98%

GTS-21 is a selective agonist at α7 nicotinic receptors with anti-inflammatory and cognition enhanc

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RGPU-95 (p-Cl-Phenylpiracetam), ≥98%RGPU-95 (p-Cl-Phenylpiracetam), ≥98%

RGPU-95 (p-Cl-Phenylpiracetam), ≥98%

RGPU-95 (p-Cl-Phenylpiracetam) is an 5x-10x more potent derivative of the nootropic compound Phenylp

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Details of Cholinergics

Cholinergics are a group of substances that mimic or modulate the action of the acetylcholine neurotransmitter. Processes, receptors and biochemical mechanisms in the body that use acetylcholine are referred to as being cholinergic. The Newmind cholinergics are all cholinergic agonists, which we will discuss further below. Cholinergic receptors respond to acetylcholine and direct-acting agonist or antagonist ligands to modulate the response of the CNS and the ANS.

The cholinergic system has been associated with a number of cognitive functions, including memory, selective attention, and emotional processing – these being in addition to the physiological function of the sympathetic/parasympathetic nervous system.1

The role of the cholinergic system in the basal forebrain and pontine areas are of particular importance to neuroscientists involved in Alzheimer’s disease and dementia research. Evidence has shown the vital role of the cholinergic system in visual attentional function, the modulation of short-term spatial memory processes, and the ability to utilize response rules through conditional discrimination.2

Cholinergics and Acetylcholine

Acetylcholine is the primary neurotransmitter in the automatic nervous system and is located predominantlyat the neuromuscular junctions, at synapse endings, and in various other places in the CNS.3 In the automatic nervous system (ANS), acetylcholine works as an internal transmitter for the sympathetic system and is the final product of the parasympathetic system.4

In the automatic nervous system, acetylcholine is an important neurotransmitter at the preganglionic sympathetic and parasympathetic neuron synapses. It is also a vital neurotransmitter for the proper functioning of the adrenal medulla and in all organs that work with the parasympathetic system. Finally, acetylcholine has an important role in the sweat glands and the piloerector muscles, causing the contraction of arrector pili.5

The role of acetylcholine in the CNS is to attenuate signal transduction through interneurons. Degenerative neural disorders affect the release of acetylcholine, which is partly why it is so useful in neuroscience research.3

Due to the importance of acetylcholine in the functioning of the body, many pharmaceutical agents, as well as many toxins and nerve agents, target cholinergic receptors. Examples include many toxins and poisons produced by bacteria, plants, and fungi. Cholinergic antagonists have an important role in surgery and anesthesia. Another example of a common cholinergic antagonist is nicotine, which is an addictive substance found in cigarettes and has strong effects on the nicotinic acetylcholine receptors.6

Cholinergics are sometimes also referred to as parasympathomimetics or cholinomimetics because of their similar action to acetylcholine. Cholinergics are studied in laboratory settings in research in combatting dementia and other neurodegenerative diseases, autoimmune diseases, and for issues with the GI tract or urinary system.7

Muscarinic vs Nicotinic Acetylcholine Receptors

The Acetylcholine receptors are divided into muscarinic (mAChRs) and nicotinic (nAChRs) groups – due to their interactions with muscarine and nicotine ligands. Muscarinic receptors are G-coupled receptors that mediate a slow-response through a secondary messenger cascade, while nicotinic receptors are ion channels that mediate fast responses and neurotransmission.8

On the one hand, muscarinic receptors interact with the muscarine toxin, found in harmless trace amounts in the Amanita muscaria mushroom but more notably found in toxic concentrations in Inocybe and Clitocybe species. The muscarine toxin causes intense stimulation of the parasympathetic nervous system which can result in convulsions and death. mAChRs are located primarily in the CNS and are involved in a large number of physiological functions including heartbeat, smooth muscle contraction, and neurotransmitter release. All five subgroups of muscarinic receptors (M1 – M5) are found in the CNS and in various tissues around the body – cardiac tissue, smooth muscles, and secretion glands.9

On the other hand, nicotinic receptors are defined by their interaction with nicotine – a common psychoactive compound most commonly associated with tobacco (Nicotiana tabacum and Nicotiana rustica) in the form of cigarette smoke. nAChRs are involved in fast-response ion-gated channels and mediate signal transduction at synapses. Nicotinic receptors are divided into two subgroups – N1/NM and N2/NN. The N1/NM receptors are located at neuromuscular junctions, while the N2/NN nAChRs are located at cholinergic and adrenergic ganglia, as well as in the CNS and the adrenal medulla.10

Cholinergic Mechanism of Action

Cholinergics have a variety of mechanisms of action. On the one hand, cholinergic agonists stimulate cholinergic receptors (including nicotinic and muscarinic receptors) to increase the activity of the parasympathetic nervous system. On the other hand, cholinergic antagonists block the action of the parasympathetic nervous system.

Cholinergic antagonists can be divided into three broad groups based on their respective mechanisms of action:

  1. The selective antagonists of muscarinic synapses of parasympathetic nerves (antimuscarinic agents). These include atropine, scopolamine, and ipratropium.
  2. Ganglionic blockers, including mecamylamine, which act selectively on the nicotinic receptors of both the parasympathetic and sympathetic nervous systems.
  3. Neuromuscular blockers, which interfere with the transmission of impulses to the skeletal muscles and have important applications in anesthesia and surgery. These include competitive blockers and depolarizing agents.11

Cholinergic agonists can be divided into two main groups:

  1. Direct cholinergic agonists, which act directly on the muscarinic and nicotinic receptors to stimulate a parasympathetic nervous system response.
  2. Indirect cholinergic agonists, which block the function of the acetylcholinesterase enzyme7

The direct acting cholinergic agonists’ effects are widespread throughout the body, due to their interactions with muscarinic receptors in the internal organs – the heart, smooth muscles, exocrine glands – and/or nicotinic receptors located in skeletal muscles.

Both direct acting and indirect acting cholinergic agonists can stimulate the muscarinic and nicotinic receptors, either by acting directly as a receptor ligand or through the deactivation of the acetylcholinesterase enzyme. Some of the studied effects of cholinergic agonists include:

- Vasodilation, decreased heart rate, and blood pressure increase/decrease
- Increased contraction of smooth muscles in the gastrointestinal tract, bronchial muscles, urinary muscles, sphincter
- Increased salivation
- Increased mucous production
- Pupil contraction12

NewMind Cholinergics

EVP-6124 HCl 98+% (Encenicline)

EVP-6124 HCl is a selective allosteric modulator of the alpha-7 nicotinic receptors (α7 nAChRs). Studies have shown that EVP-6124 does not interfere with heteromeric α4β2 nAChRs function. Research suggests an efficient mechanism of action in cognitive performance. Coadministration of EVP-6124 at 0.03 mg/kg, p.o. with donepezil at 0.1 mg/kg restored memory function in animals studies.13

Further animal studies have indicated that EVP-6124 has an excellent brain to plasma exposure ratio, and has high potency in cognitive enhancement research. EVP-6124 (0.1, 0.3, and 1.0 mg/kg) improved scopolamine-induced memory loss significantly, in a dose-dependent relationship. The combined use of AChEIs with EVP-6124 was shown to completely reverse the effects of the scolopamine neurotoxin.14

Phase 2b clinical trials on Alzheimer’s disease patients showed promising results. A 24-week study with 409 patents from both the United States and Eastern Europe met seven of the nine endpoints with statistical relevance. The study used ADAS-Cog as the primary outcome, and found a dose-dependent response to EVP-6124.15

Phase 3 clinical trials were suspended due to rare but serious gastrointestinal side effects. The phase 3 trials involved over 800 Alzheimer’s disease patients and used a higher dosage than the phase 2 trials (3mg over 2mg), which was purportedly the cause of the negative adverse effects.16

SEN 12333 / WAY-317,538 98+%

SEN 12333 (WAY-317,538) is a dual α7 nicotinic acetylcholine receptor (nAChR) agonist and histamine H3 receptor antagonist. The importance of α7 nAChRs is relevant in cognition studies, especially due to their function in regulating cholinergic neurotransmission and their down regulation in both Alzheimer’s Disease and schizophrenia. Studies have indicated that SEN 12333 / WAY-317,538 has excellent brain penetration and oral bioavailability.17

Further animal studies have elucidated the mechanism of action, showing that 5-morpholin-4-yl-pentanoic acid (4-pyridin-3-yl-phenyl)-amide (SEN 12333) has a high affinity for the rat α7 nAChRs expressed in GH4C1 cells (K(i) = 260 nM). Furthermore, SEN 12333 acts as a full agonist in Ca2+ flux studies. The compound shows no action at other nicotinic receptor sites and acts as a weak antagonist at α3 nAChRs. Cumulative results suggest that SEN 12333 has both precognitive and neuroprotective effects, in animal models.18

Centrophenoxine HCl 98+%

Centrophenoxine, also known as Meclofenoxate and sold under the brand name Lucidril, is a unique cholinergic with dimethylethanolamine (DMAE) and 4-chlorophenoxyacetic acid (pCPA) function. Animal studies have suggested an ability for Centrophenoxine to reverse lipofuscin/beta-amyloid pigmentation build-up, as well as to act as an antioxidant against lipid peroxidation. These findings have important implications in Alzheimer’s disease and dementia research and may warrant further investigations.19

Furthermore, human cell culture studies have indicated the potential application of Centrophenoxine as an agent to increase metabolism of human glial cells. Along with a reduction in accumulated lipofuscin, Centrophenoxine-treated glial cells showed improved rates of RNA and protein synthesis, as well as enhanced glucose uptake. It has been suggested that Centrophenoxine shifts the utilization of glucose from glycolysis to the pentose phosphate pathway in glial cells.20

In 1990, a clinical trial was conducted on 50 persons suffering from medium-level dementia and cognitive decline. The results showed an increase in performance in psychometric tests over the 8-weeks treatment period, as well as a significant increase in the average intracellular water content – indicating free-radical scavenging (particularly •OH) properties of meclofenoxate.21

Toxicity and Warnings

Toxicity varies for cholinergic substances found on Newmind. It is important to note that most of these chemicals lack an established human toxicity rating, and more importantly that ALL compounds offered on NewMind are strictly NOT for human consumption.

Many of the compounds do, however, have limited toxicological information available from research conducted in animal models, such as an LD-50 as determined in small mammals like mice and rats. Please read through the product listings for more in-depth toxicity research pertaining to each compound.

1 “Cholinergic System”, by Colleen E. Jackson, Encyclopedia of Clinical Neuropsychology
pp 562-564

2 BJ Everitt, TW Robbins, “Central cholinergic systems and cognition”, Annu Rev Psychol. 1997;48:649-84. 

3 “Acetylcholine”, Neuroscience 2nd Edition, Purves D, Augustine GJ, Fitzpatrick D, et al., editors.
Sunderland (MA): Sinauer Associates; 2001.

4“Parasympathetic Responses”, Boundless. "Parasympathetic Responses." Boundless Anatomy and Physiology Boundless, 24 Oct. 2016. Retrieved 31 Mar. 2017

5“Chapter 11: Acetylcholine Neurotransmission”, by Jack C. Waymire, Ph.D., Department of Neurobiology and Anatomy, The UT Medical School at Houston, available online at University of Texas online, retrieved on March 31, 2017 

6 “Cholinergic drug”, by The Editors of Encyclopedia Britannica, LAST UPDATED: 12-18-2014, available online at, retrieved on March 31, 2017

7 “Cholinergic”,, retrieved on March 31, 2017 

8 “Acetylcholine Receptors”, By Jennifer McDowall, InterPro, EMBL - The European Bioinformatics Institute, available online, retrieved March 31, 2017 

9 P Abrams et al., “Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder”, Br J Pharmacol. 2006 Jul; 148(5): 565–578, Published online 2006 Jun 5. doi:  10.1038/sj.bjp.0706780

10 F Guzman, MD, “Acetylcholine receptors: muscarinic and nicotinic”, Pharmacology Corner, available online, retrieved on March 31, 2017

11 “Cholinergic Antagonists”, Pharmacological Blog, 6/4/13, retrieved on March 31, 2017

12 “Cholinergics and Anti‐cholinergics”, by Mr. D.Raju, M.pharm,Lecturer, SRM University notes, available online, retrieved on March 31, 2017

13 J Prickaerts et al., “EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors”, Neuropharmacology. 2012 Feb;62(2):1099-110. doi: 10.1016/j.neuropharm.2011.10.024. Epub 2011 Nov 10.

14 “EVP-6124”, notes from ENCP Europe: Scientific resources for applied neuroscience,, retrieved on March 31, 2017 

15 “Experimental α7 Agonist Meets Cognitive and Clinical Endpoints”, Alzheimer's Association International Conference 2012 series, ALZforum online, retrieved on March 31, 2017

16 “Rare but Severe Side Effects Sideline Some Phase 3 Encenicline Trials”, 16 Sep 2015, ALZForum News online, retrieved on March 31, 2017 

17 SN Haydar et al., “SAR and biological evaluation of SEN12333/WAY-317538: Novel alpha 7 nicotinic acetylcholine receptor agonist”, Bioorg Med Chem. 2009 Jul 15;17(14):5247-58. doi: 10.1016/j.bmc.2009.05.040. Epub 2009 May 21. 

18 R Roncarati, “Procognitive and neuroprotective activity of a novel alpha7 nicotinic acetylcholine receptor agonist for treatment of neurodegenerative and cognitive disorders”, J Pharmacol Exp Ther. 2009 May;329(2):459-68. doi: 10.1124/jpet.108.150094. Epub 2009 Feb 17. 

19 Sharma D, Maurya AK, Singh R, “Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine”, Neurobiol Aging. 1993 Jul-Aug;14(4):319-30.

20 M Ludwig-Festl et al., “[Increase in cell metabolism in normal, diploid human glial cells in stationary cell cultures induced by meclofenoxate]”, Arzneimittelforschung. 1983;33(4):495-501.

21 T Fülöp Jr et al., “Effects of centrophenoxine on body composition and some biochemical parameters of demented elderly people as revealed in a double-blind clinical trial”, Arch Gerontol Geriatr. 1990 May-Jun;10(3):239-51.