Chemical Neuromodulation

There is a lot of interest in neuromodulation for neurological diseases. Discovering the applications, progress, and risks vs. benefits is important in understanding this process. Knowledge about development and uses can help you make decisions about your interest level in these treatments. It does not mean that you are committing to it, just that you have an understanding that will help you make informed decisions about seeking any of these treatments or if you prefer not to use them now. Knowledge is power.

Neuromodulation is chemical or electrical stimulation of selected sites of nerve activity in the body. The process can be used to help improve medical conditions. Some neuromodulation activity can speed nerve activity or nerve transmission, while others deter function. Most individuals are familiar with electrical stimulation as a neuromodulator of nerves, especially in improving nerve function. More discussion of electrical stimulation will follow next week. The less familiar term, chemical stimulation of nerves, is the topic of this blog. Some of these chemical neuromodulators will sound familiar, but you might not have thought about them in this way.

Chemical neuromodulators affect the activity of nerves or the transmission of messages by the nerves (neurotransmission), either by speeding up impulses or slowing them. There are a variety of chemical neuromodulators found naturally within the body. Sometimes, these chemicals are given to individuals through medications to control issues within the body. Only some of the major neuromodulators are presented here. Some medications affect neuromodulators by improving or slowing the functions of nerves.

Acetylcholine is a neurotransmitter in the nervous system that helps messages move from nerve to nerve in the parasympathetic nervous system. The parasympathetic nervous system is the part of the nervous system that slows body functions, especially after stressful situations. Drugs that can modulate acetylcholine are cholinergic medications and anticholinergic medications.

Cholinergic drugs mimic the function of acetylcholine in the body. These medications can help improve issues in Alzheimer’s disease, myasthenia gravis, urinary retention, paralytic ileus, glaucoma, and other issues affected by the parasympathetic nervous system. There are two types of cholinergic drugs, those that are categorized as direct-acting because they bind to muscarinic receptors, which is a direct effect on the nerve transmission process. These include methacholine, carbachol, and bethanechol. Indirect-acting cholinergic drugs increase the amount of acetylcholine produced. These drugs include the reversible drugs physostigmine, neostigmine, pyridostigmine, edrophonium, rivastigmine, donepezil, and galantamine. Irreversible drugs include echothiopate, parathion, malathion, diazinon, sarin, and soman.

Anticholinergic medications block acetylcholine function. These medications help treat Parkinson’s disease, depression, respiratory (asthma and COPD) issues, cardiovascular issues, overactive bladder, and bladder urgency. The most commonly used anticholinergic medications are tricyclic antidepressants, antihistamines (chlorpheniramine, diphenhydramine), and antimuscarinics (oxybutynin).

Serotonin is a neurotransmitter that affects mood, thinking, reward, learning, memory, pain, motor control, migraine, drug abuse, and memory, as well as vomiting and vasoconstriction (contracting of the blood vessels). It controls glutamate (a neurotransmitter that increases nerve function) and GABA (a neurotransmitter that inhibits nerve function) in the body. Drugs that affect the production of serotonin include selective serotonin reuptake inhibitors (SSRIs), and antidepressants such as citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), escitalopram (Lexapro), paroxetine (Paxil), and sertraline (Zoloft) as well as other psychiatric medications. These medications are very helpful to those who require them. However, side effects of too much serotonin in the body can include diarrhea, shivering, muscle rigidity, fever, and seizures. This is called serotonin syndrome.

Catecholamines are neurotransmitters in the body that include dopamine which inhibits complex movement, emotional response, and attention. Norepinephrine excites nerves which allows arousal, reward, dreaming, and mood regulation. Neuromodulator medications of dopamine are ergoline dopamine agonists such as bromocriptine, used to treat Parkinson’s disease, and cabergoline to treat high levels of prolactin, which is produced by the pituitary gland. Non-ergoline dopamine agonists are used to treat Parkinson’s disease (apomorphine, pramipexole, ropinirole, and rotigotine, which also treats restless leg syndrome. These medications do have risk factors so be sure to discuss use for your individual condition.

Amino Acids are neurotransmitters in the body that affect sensation, motor control, and nerve impulses. There are a wide variety of amino acid medications to assist with neuromodulation of nerve transmission. Just a few examples include drugs that inhibit amino acid function in the nerves such as opiates, cocaine, amphetamines, and, yes, caffeine. Much to many individuals’ dismay, alcohol, marijuana, and other addictive drugs affect neurotransmission by neuromodulation of nerve function producing deficits in attention, learning, memory, balance, and reaction speed.

Think about that ‘buzz’ you get after drinking alcohol or the sensation of relaxation from a joint. These sensations are neuromodulation of your body’s natural function. It is especially detrimental to the developing brain, not only fetal development but also as the brain develops as a child, teen, and young adult. There are many conflicting informational articles about this subject. However, scientific research indicates this is an effect. Some will challenge this idea, but it is substantiated.

Neuromodulators are helpful for medical conditions. Nerve impulses that produce pain can be treated by a variety of neuromodulating drugs, as neuropathic pain has many sources. Finding the right drug for your neuropathic pain may take time to discover which nerve transmissions need to be modified.

Drugs that treat neuropathic pain include anticonvulsant medications, antidepressant medications such as tricyclic antidepressants (Elavil, Sinequan, and nortriptyline), Serotonins (serotonin-norepinephrine reuptake inhibitors (SNRIs) including Cymbalta, or Effexor), SSRI including fluoxetine), capsaicin, gabapentin, pregabalin, and cannabinoids. Note that gabapentin and pregabalin have the word, ‘GABA’ contained within their names because they affect the GABA neurotransmitters.