Anticholinergics: What They Do, How They Work & Possible Uses
“Anticholinergics” are medications or other substances that either block or lower the action of the neurotransmitter acetylcholine throughout the body and mind. Some natural, plant-based anticholinergic compounds have a long history of usage in traditional types of folk medicine, whereas other, more contemporary anticholinergic drugs are routinely used by medical professionals to deal with a wide array of specific symptoms or conditions. In this informative article, we will offer a synopsis of what these compounds are, how they work and review a number of the current or potential applications of these compounds. Keep reading to learn more about the interesting science supporting these drugs!
Disclaimer: This guide is not a recommendation or endorsement for any of these drugs or other substances mentioned during this article. A number of these medications have only been FDA-approved for the treatment of certain particular health conditions, and many can only be safely and lawfully accepted by prescription and also with oversight from a licensed medical professional. We’ve written this post for informational purposes only, and our goal is to inform folks about the science behind those drugs’ effects, biological mechanisms, and potential health programs. None of the information in this informative article should ever be used to replace conventional medical care or treatment — and always be sure to discuss any new supplements or drugs with your doctor first!
What Are Anticholinergics?
The expression”anticholinergics” identifies drugs, medications, or other compounds that block the activity of the neurotransmitter acetylcholine. Broadly speaking, these chemicals bind to the very same structures (known as receptors) as acetylcholine throughout the human body, hence preventing this neurotransmitter from reaching its customary effects.
Some anticholinergics, for example, hyoscamine, are derived from plants and other natural sources. As an example, the fruit and leaves of the plant Atropa Belladonna (atropine), sometimes also known as”Deadly Nightshade,” are believed to have anticholinergic effects.
Other, “artificial” anticholinergic agents comprise ipratropium bromide (Atrovent), doxepin, tadalafil, diphenhydramine, among many others. These anticholinergics are sometimes used to treat respiratory ailments (such as asthma and asthma ), as well as more complicated health ailments, such as melancholy, sleeplessness, irritable bowel syndrome (IBS), and motion sickness. Some synthetic anticholinergics have also been proposed to possibly help relieve certain symptoms of Parkinson’s disease and overactive bladder.
However, using anticholinergics comes with specific risks — particularly when taken in excess. These include lots 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 also have been reported by individuals to cause skin rashes, elevated body temperature (hyperthermia), and tingling of the mouth or skin.
In the remainder of this post, we’ll review the scientific and historical background behind these anticholinergic compounds, how they operate, and a number of the several possible medical and other applications that were suggested by researchers. To learn more about the many potential side-effects, drug interactions, and other possible dangers associated with the use of anticholinergic compounds.
Mechanism of Action
Generally, the neurotransmitter acetylcholine binds to and activates two distinct receptors within the human body: nicotinic and muscarinic acetylcholine receptors.
“Nicotinic receptors” obtained their name because they’re activated by the medication nicotine. In contrast,” muscarinic receptors” get their name from the fact they are triggered by a poison from mushrooms called muscarinic acid. Anticholinergics work on the contrary way: by blocking the two of these kinds of acetylcholine receptors.
Acetylcholine has a huge array of important functions throughout the body and brain. By way of example, it serves as the”final messenger” for the parasympathetic system, which counteracts the”fight-or-flight” response. Acetylcholine is therefore accountable for maintaining the body in a condition of rest, digestion, and regeneration utilizing the muscarinic pathway, which includes five major receptor subtypes (M1-M5). Surplus acetylcholine can also bring about overactivation of the muscarinic system, which may give rise to inflammation in certain ailments, such as in asthma. This is also why drugs that block muscarinic receptors in the lungs have been used to treat these ailments, as they can help relax the airways, thus allowing for better breathing.
Other “anti-muscarinic” drugs, such as those generally used to treat overactive bladder, block specific muscarinic receptors (mostly M2 and M3). However, these medications can also sometimes cause undesirable side-effects elsewhere, such as dry mouth or headaches.
Acetylcholine is also utilized to activate muscles utilizing the nicotinic pathway: consequently, drugs that block this pathway may cause paralysis and are sometimes used during anesthesia.
Types of Anticholinergics
Muscarinic Anticholinergics
Muscarinic receptors are found primarily within the brain and spinal cord, in addition to in the muscles controlled by the parasympathetic nervous system, including the bladder, lungs, heart, and airway muscles.
Ipratropium, scopolamine, and glycopyrrolate are examples of muscarinic anticholinergics.
Muscarinic anticholinergics are commonly utilized to treat bronchitis, asthma, motion sickness, and occasionally even fear. Additionally, they sometimes behave as “antidepressants,” and also have been reported to help prevent the noxious effects of particular nerve agents and other toxins.
Muscarinic anticholinergics may also be referred to by different names, including antimuscarinics, muscarinic antagonists, and muscarinic cholinergic antagonists.
Nicotinic Anticholinergics
Nicotinic receptors are mainly located at the links between nerves and skeletal muscles. Blocking these receptors can, therefore, interfere with movement, and — in high-enough doses — may even bring about paralysis.
This is the reason why curare, a natural nicotinic anticholinergic, was used in hunting for centuries. Finally, scientists began to find out more about the physiological mechanisms of curare, and its first medical program was supposed to assist in preventing muscle contractions through surgery. Research into curare’s mechanics finally allowed for the evolution of further artificial alternatives, with similar actions and effects.
Pancuronium and mecamylamine are cases of nicotinic receptor blockers.
Pancuronium is a muscle relaxant used in anesthesia. By comparison, mecamylamine subdues the consequences of alcohol and has been used to fight cigarette and alcohol addiction. Mecamylamine has also been reported to possess some “antidepressive” effects.
Mecamylamine was widely utilized as a treatment for elevated blood pressure (hypertension). But, that’s rarely the case now, because of the elevated rate of side-effects caused by the required dose.
Nicotinic anticholinergics may also be known as antinicotinic or nicotinic antagonists.
14 Possible Uses of Anticholinergics
In the sections below, we will go over many different proposed medical or therapeutic applications for anticholinergic compounds and drugs, and what the latest science has to say about these.
Before we start, however, it is essential to be aware that not all these medications have been approved for each application or specific medical condition discussed in the sections below. Furthermore, many of the drugs we talk in the sections below require a prescription and supervision from a medical professional to be obtained safely and legally.
Consequently, if you have any of these health conditions — or even if you have some other pertinent questions about these potential applications of anticholinergics — then we strongly advise discussing them completely with your doctor, who can help further inform you about any potential therapeutic benefits or risks associated with any particular course of treatment. The data in this post should not otherwise be applied as a replacement for conventional medical care or treatment, as only a fully-qualified medical practitioner has the necessary training and background to devise a treatment plan that is fully-suited for your individual medical history and needs.
Relatedly, it ought to be kept in mind that a number of the potential applications below have been proposed on the basis of scientific evidence that is still in a comparatively early stage. For instance, much of the preliminary study comes from studies in animals and cell cultures, instead of complete clinical trials in human patients. Therefore, the uses outlined below must be considered to currently have “insufficient evidence” until considerable amounts of further research is done — notably from studies in massive samples of human users.
With all this in mind, let’s see what some of the most recent science has to say regarding the potential applications of anticholinergic compounds, in addition to the possible mechanisms responsible for their effects!
1) Respiratory Diseases and Conditions
Chronic Obstructive Pulmonary Disease (COPD)
According to one study, inhalers full of tiotropium were reported to improve respiration in 470 patients with chronic obstructive pulmonary disease (COPD). It also reportedly reduced other ailments, like wheezing and shortness of breath.
In another study of 20 elderly men with COPD, a number of different anticholinergic compounds — such as ipratropium, flutropium, and oxitropium bromide — were reported to help relax the respiratory pathways. The patients in this study reported undergoing easier breathing from all treatments, although oxitropium bromide was ultimately concluded to be the most effective remedy for this particular purpose.
Muscarinic anticholinergics are used more commonly in COPD than steroid remedies, since they are reported to have longer-lasting effects on respiratory channels, and generally require only one daily dose to cause improved symptoms.
Asthma
Based on 15 clinical trials at a total of over 7,000 human patients having asthma, long-acting muscarinic anticholinergics were reported to enhance asthma symptoms (when combined with other corticosteroid drugs).
Moreover, the usage of muscarinic anticholinergics as an add-on treatment for asthma has been associated with decreased long-term rates of asthma attacks.
Bronchitis
Comparable to asthma treatment, inhaled muscarinic anticholinergics are reported to facilitate breathing in patients — and might even double breathing capability in some patients. In the last several decades, muscarinic anticholinergics like ipratropium bromide (Atrovent) are used to manage the daily symptoms of bronchitis.
2) Depression
Tricyclic antidepressants (TCAs) are one type of medication used in melancholy and have been reported to demonstrate some anticholinergic activity. According to 5 human research, up to 56-60% of depression patients had been reported to react favorably to TCAs, which reduced general depression symptom rating scores in addition to the number of reported adverse side-effects.
Scopolamine (at a dosage of 4.0 µg/kg) was reported to rapidly reduce symptoms of depression in 52 issues (31 male, 21 female) with depression or bipolar disorder. In a second analysis, scopolamine was reported to have a relatively long-lasting effect (over 2 weeks after treatment), though female patients reported experiencing higher symptom improvements compared to guys.
The nicotinic anticholinergic mecamylamine, along with other antidepressants (selective serotonin reuptake inhibitors, commonly called “SSRIs”), has been reported to boost treatment-resistant melancholy (TRD) according to 2 Phase-II clinical trials.
3) Anesthesia
Pancuronium is a muscle relaxant that’s sometimes used during anesthesia. According to some research, pancuronium may be particularly useful during heart surgeries: for example, it causes significantly fewer undesirable side-effects (for example, adverse changes in heart rate or blood pressure) when compared to other muscle relaxants, for example, vecuronium and pipecuronium.
Other anticholinergic drugs, for example, glycopyrrolate, are also sometimes administered prior to or during surgery. Some research indicates that it might be considerably more powerful than other anticholinergics, like atropine, and has also been reported to cause fewer adverse side-effects, such as irregular heartbeats and other cardiovascular complications.
4) Irritable Bowel Syndrome (IBS)
Based on three studies in a total of 426 patients, the anticholinergic hyoscine (also known as scopolamine butylbromide) allegedly reduced symptoms of irritable bowel syndrome (IBS) in comparison with placebo therapy. Patients either reported improved symptoms or in some cases the complete disappearance of abdominal pain.
Hyoscine has also been reported to decrease cramping pain, according to 10 clinical studies. Even though the exact mechanisms involved are not known, some researchers think it might achieve its effects chiefly by relaxing the muscles of the stomach and intestines.
5) Quitting Smoking
The combination of both mecamylamine and nicotine patches has been reported to be better than just nicotine patches alone for smoking cessation. As an 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 individuals succeeded in abstaining from smoking for one year, compared to 20% of patients who received other treatments.
Although the mechanisms of the effects have yet to be completely discovered yet, some evidence indicates that mecamylamine may help smoking cessation by lowering the pleasurable (“rewarding” or”strengthening”) sensations associated with smoking. By way of instance, 1 study reported that chronic smokers reported significantly reduced feelings of personal reward from smokes after just two weeks of therapy.
6) Overactive Bladder and Abdominal Pain
Anticholinergics are often the first choice of medication for treating overactive bladder.
Anticholinergics — especially when used in conjunction with other medications (such as alpha-adrenergic antagonists) — are widely considered to be a generally safe and effective method for treating overactive bladder and abdominal pain.
Even though the exact mechanisms aren’t fully known yet, some researchers have suggested that these therapies may work primarily by relaxing the muscles of the bladder.
According to one review of 32 clinical trials involving 6,800 participants with overactive bladder, anticholinergics were reported to generate substantial improvements in symptoms (in comparison with inactive placebo treatments).
Another review of 50 clinical trials (including data from 27,000 patients) reasoned that anticholinergics were effective for partly improving symptoms of the overactive bladder — however, the writers of this review also concluded that these effects were not strong enough to make anticholinergics alone the sole remedy method.
7) May Counteract Negative Outcomes of Alcohol
Some interesting preliminary research indicates that anticholinergics can”block” a number of the severe effects of alcohol intoxication.
For instance, one study noted that the anticholinergic mecamylamine decreased breath alcohol levels (BAL) in 20 healthy subjects, compared to inactive placebo therapy. Additionally, mecamylamine treatment before consuming 3 alcoholic drinks was reported to decrease the pleasurable sense of”benefit” experienced because of alcohol ingestion.
However, it is crucial to note that these consequences are restricted only to certain specific, individual serious effects of alcohol, and such early findings don’t suggest that anticholinergics can completely “block” or “counteract” the alcohol total intoxicating results! Instead, these findings are useful more in the meaning that they help narrow down that of alcohol effects may be mediated by acetylcholine-related mechanisms, as they can reportedly be influenced by anticholinergics. In other words, these preliminary reports shouldn’t be taken to suggest that an individual could somehow “cancel out” the consequences of drinking by swallowing anticholinergic compounds.
8) Insomnia
According to a 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 allegedly enhanced sleep duration, sleep quality, and sleep care in these patients.
In a controlled study in 110 subjects with mild-to-moderate insomnia, a 50mg dosage of the anticholinergic medication diphenhydramine was reported to significantly lessen the amount of time that these patients needed to fall asleep.
9) May Counteract Some Side-Effects of Antipsychotic Drugs
Antipsychotic medications can occasionally cause motor signs (“extrapyramidal symptoms”), for example, stiffened muscles or uncontrollable muscle contractions. Anticholinergic agents (including the medication diphenhydramine) are usually added on as pharmaceutical treatments in movement disorders (especially dystonia).
According to a review of 4 research containing data in a total of 737 subjects, diphenhydramine was reported to decrease the number of motor symptoms induced by antipsychotic medications.
10) Enlarged Prostate
According to a preliminary single-blind control analysis, the anticholinergic medication tadalafil reportedly improved the condition of 281 men with benign enlargements of the prostate. Some sexually-active guys in the treatment group also reported improved erectile function, even though the significance of this result isn’t completely clear.
11) May Prevent Nausea or Motion Sickness
Some anticholinergics, for example, hyoscine and scopolamine (scopolamine butyl bromide), have already been reported to counteract signs of vertigo. Vertigo is believed to be induced — in part — by illusory or”hallucinatory” sensations of movement which arise from abnormal action from the motion sensors of the inner ear. Some researchers have suggested that anticholinergics may relieve vertigo by targeting those”motion sensors,” although this idea has yet to be completely confirmed by appropriate clinical trials.
According to a review of 14 clinical studies (such as data from 1,025 participants), the anticholinergic scopolamine was reported to prevent motion sickness compared to inactive placebo treatment.
In a randomized control study, dimenhydrinate (also called the over-the-counter medication Dramamine) was reported to decrease feelings of nausea in 70 girls during the first stages of pregnancy. As per a follow-up study in 70 other elderly ladies, dimenhydrinate was likewise reported to be more effective than therapy with vitamin B6.
12) May Help Manage Parkinson’s Disease Symptoms
According to one review of information from 221 Parkinson’s disease patients that engaged 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 signs (in comparison to combined treatment with an inactive placebo).
13) May Prevent Excessive Sweating in Anxiety
Excessive sweating (hyperhidrosis) is a relatively common symptom of stress disorders and can cause additional distress to patients with these disorders.
According to a preliminary controlled trial, the anticholinergic medication glycopyrrolate was reported to decrease symptoms of excessive sweating in 36 patients with anxiety disorders. This treatment was associated with reduced symptoms of anxiety, in addition to patient reports of increased overall quality-of-life.
14) May Counteract Nerve Agents or alternative Toxins
According to some ancient studies in animals, anticholinergic drugs might be able to partly counteract some of these toxic effects of nerve agents and other toxins.
But due in substantial part to ethical limitations about analyzing these compounds in humans, the preliminary evidence for these effects comes solely from animal studies and hasn’t been directly detected or confirmed in human inhabitants.
According to one such creature research, three distinct 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 have been reported to significantly slow down the toxicity of nerve agent exposure.
Another animal study reported that the anticholinergic medication atropine and homatropine partially reduced the toxic effects of sarin gas placed on the eyes of rats, which in turn partially protected their eyesight. Since sarin gas and other nerve agents have historically been used (illegally) in war, some researchers have indicated that these medications might be potentially useful for soldiers who may be subjected to those highly-toxic nerve agents on the battlefield.
Similarly, another study in rats reported that eye drops containing the anticholinergic medication 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 fully reversed within just four hours, as the pupils widened and vision returned (as tested by a behavioral test of visual perception).
