“Anticholinergics” are drugs or other substances that either block or reduce the activity of the neurotransmitter acetylcholine throughout the body and brain. Some natural, plant-based anticholinergic compounds have a long history of use in traditional forms of folk medicine, while other, more modern anticholinergic drugs are routinely used by medical professionals to treat a wide variety of specific symptoms or conditions. In this post, we’ll provide an overview of what these compounds are, how they work, and review some of the current or potential applications of these compounds. Read on to learn more about the interesting science behind these drugs!
Disclaimer: This article is not a recommendation or endorsement for any of the drugs or other compounds mentioned throughout this post. Many of these medications have only been FDA-approved for the treatment of certain specific medical conditions, and most can only be safely and legally taken by prescription and with oversight from a licensed medical professional. We have written this post for informational purposes only, and our goal is solely to inform people about the science behind these drugs’ effects, biological mechanisms, and potential health applications. None of the information in this post should ever be used to replace conventional medical care or treatment — and always be sure to discuss any new supplements or medications with your doctor first!
What Are Anticholinergics?
The term “anticholinergics” refers to medications, drugs, or other compounds that block the activity of the neurotransmitter acetylcholine. Generally speaking, these compounds bind to the same structures (known as receptors) as acetylcholine throughout the body, thereby preventing this neurotransmitter from achieving its usual effects [1, 2].
Some anticholinergics, such as hyoscamine, are derived from plants and other natural sources. For example, the fruit and leaves of the plant Atropa Belladonna (atropine), sometimes also known as “Deadly Nightshade,” are believed to have anticholinergic effects [3, 4].
Other, “synthetic” anticholinergic agents include ipratropium bromide (Atrovent), doxepin, tadalafil, diphenhydramine, among many others. These anticholinergics are sometimes used to help treat respiratory disorders (such as asthma and bronchitis), as well as more complex health conditions, such as depression, insomnia, irritable bowel syndrome (IBS), and motion sickness. Some synthetic anticholinergics have also been proposed to potentially help relieve certain symptoms of Parkinson’s disease and overactive bladder [5, 6, 7, 8, 9, 10, 11].
However, the use of anticholinergics also comes with certain risks — especially if taken in excess. These include a number of side-effects ranging from increased heart rate (tachycardia), elevated blood pressure (hypertension), blurred vision, and impaired digestion, to more serious side-effects such as delirium, dementia, and even coma. They have also been reported by patients to cause skin rashes, elevated body temperature (hyperthermia), and dryness of the mouth or skin [12, 13].
In the rest of this post, we’ll review the historical and scientific background behind these anticholinergic compounds, how they work, and some of the various potential medical and other applications that have been proposed by researchers. For more information on the various potential side-effects, drug interactions, and other possible risks associated with the use of anticholinergic compounds, see part 2 of our SelfHacked series on anticholinergics here.
Mechanism of Action
In general, the neurotransmitter acetylcholine binds to and activates two different receptors in the body: nicotinic and muscarinic acetylcholine receptors.
“Nicotinic receptors” got their name because they are activated by the drug nicotine. In contrast, “muscarinic receptors” get their name from the fact that they are activated by a poison from mushrooms called muscarinic acid. Anticholinergics function in the opposite way: by blocking both of these types of acetylcholine receptors [14, 2].
Acetylcholine has a wide variety of important functions throughout the body and brain. For example, it serves as the “final messenger” for the parasympathetic system, which counteracts the “fight-or-flight” response. Acetylcholine is therefore also responsible for keeping the body in a state of rest, digestion, and regeneration using the muscarinic pathway, which has five main receptor subtypes (M1-M5). Excess acetylcholine can also cause overactivation of the muscarinic system, which may contribute to inflammation in some diseases, such as in asthma. This is also why drugs that block muscarinic receptors in the lungs are used to treat these conditions, as they can help relax the airways, thus allowing for better breathing .
Other “anti-muscarinic” medications, such as those commonly used to treat overactive bladder, block specific muscarinic receptors (mostly M2 and M3). However, these medications can also sometimes cause unwanted side-effects elsewhere, such as dry mouth or headaches .
Acetylcholine is also used to activate muscles using the nicotinic pathway: therefore, drugs that block this pathway can induce paralysis, and are sometimes used during anesthesia .
Types of Anticholinergics
Muscarinic receptors are located primarily within the brain and spinal cord, as well as in the muscles controlled by the parasympathetic nervous system, including the bladder, heart, lungs, and airway muscles [14, 18, 19].
Muscarinic anticholinergics are commonly used to treat bronchitis, asthma, motion sickness, and occasionally even anxiety. Additionally, they sometimes act as “antidepressants,” and have also been reported to help prevent the toxic effects of certain nerve agents and other toxins [20, 23, 24, 10].
Muscarinic anticholinergics can also be referred to by different names, such as antimuscarinics, muscarinic antagonists, and muscarinic cholinergic antagonists.
Nicotinic receptors are mainly located at the connections between nerves and skeletal muscles. Blocking these receptors can, therefore, interfere with movement, and — in high-enough doses — can even cause paralysis [14, 25].
This is why curare, a natural nicotinic anticholinergic, was historically used in hunting for centuries. Eventually, scientists began to research the physiological mechanisms of curare, and its earliest medical application was to help prevent muscle contractions during surgery. Research into curare’s mechanisms eventually allowed for the development of additional synthetic alternatives, with similar activity and effects [14, 25].
Pancuronium is a muscle relaxant used in anesthesia. In contrast, mecamylamine subdues the effects of alcohol, and has been used to help fight alcohol and cigarette addiction. Mecamylamine has also been reported to have some “antidepressive” effects [26, 27, 28, 29].
Mecamylamine was once widely used to treat elevated blood pressure (hypertension). However, that is rarely the case now, due to the high rate of side-effects caused by the required dosage .
Nicotinic anticholinergics can also be referred to as antinicotinic or nicotinic antagonists.
14 Potential Uses of Anticholinergics
In the sections below, we’ll discuss a variety of different proposed medical or therapeutic applications for anticholinergic compounds and drugs, and what the latest science has to say about them.
Before we begin, however, it is important to note that not all of these drugs have been officially approved for each application or specific medical condition discussed in the sections below. Additionally, many of the drugs we discuss in the sections below require a prescription and oversight from a medical professional to be taken safely and legally.
Therefore, if you have any of the following health conditions — or if you have any other relevant questions about these potential applications of anticholinergics — then we strongly recommend discussing them thoroughly with your doctor, who can help further inform you about any potential therapeutic benefits or risks associated with any particular course of treatment. The information in this post should not otherwise be used as a replacement for conventional medical care or treatment, as only a fully-qualified medical professional has the necessary background and training to devise a treatment plan that is fully-suited to your individual medical history and needs.
Relatedly, it should be kept in mind that many of the potential applications below have been proposed on the basis of scientific evidence that is still in a relatively early stage. For example, much of this preliminary research comes from studies in animals and cell cultures, rather than full clinical trials in human patients. Therefore, the uses outlined below should be considered to currently have “insufficient evidence” until significant amounts of additional research is performed — especially from studies in large samples of human users.
With all that in mind, let’s see what some of the latest science has to say about the potential uses of anticholinergic compounds, as well as the potential mechanisms responsible for their effects!
1) Respiratory Diseases and Conditions
Chronic Obstructive Pulmonary Disease (COPD)
According to one study, inhalers filled with tiotropium were reported to improve respiration in 470 patients with chronic obstructive pulmonary disease (COPD). It also reportedly reduced other symptoms, such as wheezing and shortness of breath .
In another study of 20 elderly men with COPD, a variety of different anticholinergic compounds — including ipratropium, flutropium, and oxitropium bromide — were reported to help relax the respiratory pathways. The patients in this study reported experiencing easier breathing from all treatments, although oxitropium bromide was ultimately concluded to be the most effective treatment for this purpose .
Muscarinic anticholinergics are used more commonly in COPD than steroid treatments, as they are reported to have longer-lasting effects on respiratory channels, and usually require only a single daily dose to result in improved symptoms [20, 33].
According to 15 clinical trials in a total of over 7,000 individual patients with asthma, long-acting muscarinic anticholinergics were reported to improve asthma symptoms (when combined with other corticosteroid drugs) .
Additionally, the use of muscarinic anticholinergics as an add-on therapy for asthma has been associated with reduced long-term rates of future asthma attacks .
Similar to asthma treatment, inhaled muscarinic anticholinergics have been reported to ease breathing in bronchitis patients — and may even double breathing capacity in some patients. In recent years, muscarinic anticholinergics such as ipratropium bromide (Atrovent) have been used to help manage the daily symptoms of bronchitis [35, 36].
Tricyclic antidepressants (TCAs) are one class of drugs used in depression, and have been reported to show some anticholinergic activity. According to 5 human studies, up to 56-60% of depression patients were reported to respond positively to TCAs, which reduced overall depression symptom rating scores as well as the number of reported negative side-effects [37, 38].
Scopolamine (at a dosage of 4.0 µg/kg) was reported to rapidly reduce symptoms of depression in 52 subjects (31 male, 21 female) with depression or bipolar disorder. In another study, scopolamine was reported to have a relatively long-lasting effect (over 2 weeks after treatment), although female patients reported experiencing greater symptom improvements than men .
The nicotinic anticholinergic mecamylamine, along with other antidepressants (selective serotonin reuptake inhibitors, commonly known as “SSRIs”), has been reported to improve treatment-resistant depression (TRD) according to two Phase-II clinical trials .
Pancuronium is a muscle relaxant that is sometimes used during anesthesia. According to some studies, pancuronium may be particularly useful during heart surgeries: for example, it causes significantly fewer unwanted side-effects (such as adverse changes in heart rate or blood pressure) when compared to other muscle relaxants, such as vecuronium and pipecuronium [26, 40].
Other anticholinergic drugs, such as glycopyrrolate, are also sometimes administered before or during surgery. Some research indicates that it may be significantly stronger than other anticholinergics, such as atropine, and has also been reported to lead to fewer adverse side-effects, such as irregular heartbeats and other cardiovascular complications [22, 41].
4) Irritable Bowel Syndrome (IBS)
According to three studies in a total of 426 patients, the anticholinergic hyoscine (also known as scopolamine butylbromide) reportedly reduced symptoms of irritable bowel syndrome (IBS) compared to placebo treatment. Patients either reported improved symptoms, or in some cases the complete disappearance of abdominal pain .
Hyoscine has also been reported to reduce cramping pain, according to 10 clinical studies. Although the precise mechanisms involved are not known, some researchers believe that it may achieve its effects primarily by relaxing the muscles of the stomach and intestines .
5) Quitting Smoking
The combination of mecamylamine and nicotine patches has been reported to be better than just nicotine patches alone for smoking cessation. For example, one study of 48 subjects reported that about 40% of the patients given the combination treatment successfully stopped smoking, compared to only about 4% of patients who used only nicotine patches. According to another study of 80 patients, 40% of patients succeeded in abstaining from smoking for one year, compared to 20% of patients who received other treatments .
Although the mechanisms of these effects have not been fully discovered yet, some evidence suggests that mecamylamine may aid smoking cessation by reducing the pleasurable (“rewarding” or “reinforcing”) sensations associated with smoking. For example, one study reported that chronic smokers reported significantly reduced feelings of personal reward from cigarettes after just two weeks of treatment .
6) Overactive Bladder and Abdominal Pain
Anticholinergics are often the first choice of drugs for treating overactive bladder.
Anticholinergics — especially when used in combination with other drugs (such as alpha-adrenergic antagonists) — are widely considered to be a generally safe and effective method for treating overactive bladder and abdominal pain .
Although the exact mechanisms are not fully known yet, some researchers have proposed that these treatments may work primarily by relaxing the muscles of the bladder .
According to one review of 32 clinical trials including 6,800 participants with overactive bladder, anticholinergics were reported to produce significant improvements in symptoms (as compared to inactive placebo treatments) .
Another review of 50 clinical trials (including data from ~27,000 patients) concluded that anticholinergics were effective for partially improving symptoms of overactive bladder — however, the authors of this review also concluded that these effects were not strong enough to make anticholinergics alone the sole treatment method .
7) May Counteract Some Effects of Alcohol
Some interesting preliminary research suggests that anticholinergics may “block” some of the acute effects of alcohol intoxication.
For example, one study reported that the anticholinergic mecamylamine reduced breath alcohol levels (BAL) in 20 healthy subjects, compared to an inactive placebo treatment. Additionally, mecamylamine treatment prior to consuming 3 alcoholic beverages was reported to reduce the pleasurable sense of “reward” experienced due to alcohol consumption .
However, it is important to note that these effects are limited only to certain specific, individual acute effects of alcohol, and these early findings do not imply that anticholinergics can completely “block” or “counteract” the alcohol’s overall intoxicating effects! Rather, these findings are useful more in the sense that they help narrow down which of alcohol’s effects might be mediated by acetylcholine-related mechanisms, since they can reportedly be influenced by anticholinergics. In other words, these preliminary reports should not be taken to suggest that a person could somehow “cancel out” the effects of drinking by consuming anticholinergic compounds.
According to one preliminary study, doxepin — a tricyclic antidepressant (TCA) with anticholinergic effects — was reported to improve sleep patterns and quality-of-life in 130 elderly adults with chronic insomnia. It also reportedly enhanced sleep duration, sleep quality, and sleep maintenance in these patients .
In a controlled study in 110 subjects with mild-to-moderate insomnia, a 50mg dosage of the anticholinergic drug diphenhydramine was reported to significantly reduce the amount of time these patients needed to fall asleep .
9) May Counteract Some Side-Effects of Antipsychotic Drugs
Antipsychotic medications can sometimes cause motor symptoms (“extrapyramidal symptoms”), such as stiffened muscles or uncontrollable muscle contractions. Anticholinergic agents (such as the drug diphenhydramine) are often added on as pharmaceutical treatments in movement disorders (especially dystonia) [48, 49, 50, 51].
According to a review of 4 studies including data from a total of 737 subjects, diphenhydramine was reported to reduce some of the motor symptoms induced by antipsychotic medications .
10) Enlarged Prostate
According to one preliminary single-blind control study, the anticholinergic medication tadalafil reportedly improved the condition of 281 men with benign enlargements of the prostate. Some sexually-active men in the treatment group also reported improved erectile function, although the significance of this effect is not entirely clear .
11) May Prevent Nausea or Motion Sickness
Some anticholinergics, such as hyoscine and scopolamine (scopolamine butylbromide), have been reported to counteract symptoms of vertigo. Vertigo is believed to be caused — at least in part — by illusory or “hallucinatory” sensations of motion that arise from abnormal activity in the motion sensors of the inner ear. Some researchers have proposed that anticholinergics may alleviate vertigo by targeting these “motion sensors,” although this idea has yet to be fully confirmed by appropriate clinical studies .
According to one review of 14 clinical studies (including data from 1,025 participants), the anticholinergic scopolamine was reported to prevent motion sickness compared to an inactive placebo treatment .
In one randomized control study, dimenhydrinate (also known as the over-the-counter medication Dramamine) was reported to reduce feelings of nausea in 70 women during the early stages of pregnancy. According to a follow-up study in 70 other pregnant women, dimenhydrinate was also reported to be more effective than treatment with vitamin B6 .
12) May Help Manage Parkinson’s Disease Symptoms
According to one review of data from 221 Parkinson’s disease patients who participated in clinical trials to control their motor symptoms, combining anticholinergic drugs with more conventional Parkinson’s medications was reported to significantly improve the patients’ motor symptoms (compared to combined treatment with an inactive placebo) .
13) May Prevent Excessive Sweating in Anxiety
Excessive sweating (hyperhidrosis) is a relatively common symptom of anxiety disorders, and can cause additional distress to patients with these disorders.
According to one preliminary controlled trial, the anticholinergic drug glycopyrrolate was reported to reduce symptoms of excessive sweating in 36 patients with anxiety disorders. This treatment was also associated with reduced symptoms of anxiety, as well as patient reports of increased overall quality-of-life .
14) May Counteract Nerve Agents or Other Toxins
According to some early studies in animals, anticholinergic medications may be able to partially counteract some of the toxic effects of nerve agents and other toxins.
However, due in large part to ethical limitations about testing these compounds in humans, the preliminary evidence for these effects come solely from animal studies, and have not been directly observed or confirmed in human populations.
According to one such animal study, three different anticholinergic drugs (benactyzine, biperiden, and scopolamine) were reported to protect rats against the toxic effects of the nerve agent tabun. In follow-up assessments of the rats’ symptoms at 24 hours and 7 days post-injection, these drugs were reported to significantly slow down the toxicity of nerve agent exposure .
Another animal study reported that the anticholinergic drugs atropine and homatropine partially reduced the toxic effects of sarin gas applied to the eyes of rats, which in turn partially protected their vision. Because sarin gas and other nerve agents have historically been used (illegally) in war, some researchers have suggested that these drugs may be potentially useful for soldiers who may be exposed to these highly-toxic nerve agents on the battlefield [55, 56].
Similarly, another study in rats reported that eye drops containing the anticholinergic drug tropicamide effectively reversed the toxic effects of sarin gas exposure. According to the study’s authors, the visual impairments caused by the nerve agent were completely reversed within just 4 hours, as the pupils widened and eyesight returned (as tested by a behavioral test of visual perception) .
Now that you’re up to speed on the general background of anticholinergics, how they work, and some of their potential uses, you might be curious to learn more about the various potential risks and dangers associated with their use! In part 2 of our SelfHacked series on anticholinergics, we’ll review what some of the latest science has to say about their potential side-effects, drug interactions, and other possible risks.