Learning Outcomes
By the end of this section, you should be able to:
- 9.3.1 Describe the main neurotransmitters and their functions.
- 9.3.2 Define characteristics of drugs to treat nervous system disorders.
Neurotransmitters
Neurotransmitters play a crucial role in the communication between neurons in the nervous system. Neurotransmitters are chemical messengers that transmit signals across the chemical synapses, enabling various functions and processes in the body, including signaling to release neurotransmitter molecules. Synapses are composed of three components: the presynaptic terminal, the post-synaptic terminal, and the synaptic cleft. Synaptic vesicles, containing neurotransmitter molecules, are located on the presynaptic terminal at the end neuron’s axon. Subsequently, the postsynaptic terminal uses specialized protein receptors to bind to these neurotransmitters. Neurotransmitters result in an action, inaction, or inhibition of a neuron (see Figure 9.6). When neurotransmitter levels are imbalanced or disrupted, it can lead to pathological conditions and disorders.
It is important to note that neurotransmitter imbalances are just one aspect of the complex mechanisms underpinning pathological conditions. Many disorders involve a combination of genetic, environmental, and neurochemical factors. Diagnosis and treatment of these conditions often require a comprehensive approach involving various therapies and medications targeting specific neurotransmitter systems.
The main neurotransmitters of the nervous system, function, and potential pathology are shown in Table 9.1. (The items in the “Potential Pathology” column are provided as examples, not as an exhaustive list.)
| Neurotransmitter | Function | Potential Pathology |
|---|---|---|
| Acetylcholine |
|
Low levels of acetylcholine have been noted in Alzheimer’s disease and myasthenia gravis. |
| Norepinephrine |
|
Imbalances in norepinephrine levels have been associated with various disorders, including attention deficit hyperactivity disorder (ADHD) and mood disorders. |
| Dopamine |
|
Imbalanced levels of dopamine have been associated with psychiatric and neurological disorders, including schizophrenia, depression, and Parkinson’s disease. |
| Serotonin |
|
Serotonin pathology is typically associated with depression but is also associated with bowel motility, bladder control, and cardiovascular function. |
| Histamine |
|
Histamine plays a role in asthma, bronchospasm, and mucosal edema as well as multiple sclerosis. |
| Gamma-aminobutyric acid (GABA) |
|
GABA, considered primarily an inhibitory neurotransmitter, has been implicated in anxiety disorders, epilepsy, and sleep disorders. |
| Glutamate |
|
Glutamate is the primary excitatory neurotransmitter; its dysfunction has been related to Alzheimer’s disease and Parkinson’s disease. |
Nervous System Drug Properties
The primary neurotransmitters of the PNS are acetylcholine, norepinephrine, and epinephrine.
Nerves that release acetylcholine are called cholinergic nerves. Nicotinic receptors and muscarinic receptors are the two subtypes of cholinergic receptors. Cholinergic receptor activation results in tachycardia, hypertension, increased tone, and motility of the digestive tract. Drugs that increase or stimulate the release of acetylcholine are known as parasympathomimetic due to their mimicking of the parasympathetic nervous system. Drugs that block acetylcholine are known as anticholinergic, cholinergic-blocking, or parasympatholytic and result in inhibition of the parasympathetic nervous system and sympathetic nervous system induction.
Adrenergic receptors mediate the response to epinephrine (adrenaline) and norepinephrine. The subtypes of adrenergic receptors are the alpha receptors (alpha1 and alpha2) and beta receptors (beta1, beta2, and beta3). Adrenergic drugs, also referred to as sympathomimetics, mimic the sympathetic nervous system response. Adrenergic antagonists block adrenergic receptors and reduce the effects of norepinephrine. Some drugs may target the activation of one receptor or activate multiple receptors. See Table 9.2 for an overview of autonomic receptors and subsequent responses.
| Primary Neurotransmitter | Receptor | Response |
|---|---|---|
| Norepinephrine | Alpha1 | Mydriasis (pupil dilation), smooth muscle contraction |
| Alpha2 | Inhibited norepinephrine release | |
| Beta1 | Increased heart rate, increased heart contraction force, renin release | |
| Beta2 | Smooth muscle inhibition | |
| Beta3 | Increased lipolysis | |
| Acetylcholine | Nicotinic | Stimulates smooth muscle and gland secretions |
| Muscarinic | Decreased heart rate and heart contraction force |
Autonomic Nervous System Stimulant and Blocker Characteristics
Any pathological process that causes a disruption in the homeostasis between the SNS and the PNS may cause one of these branches to become overexcited while causing the other system to be extremely inhibited (Clar & Sharma, 2023). A wide range of symptoms may occur due to this disruption in homeostasis, and medications may be used to restore homeostasis. There are four groups of medications that are used to restore homeostasis between the SNS and PNS, and they are classified on how they affect the ANS (Clar & Sharma, 2023):
- Cholinomimetics/cholinesterase antagonists include medications that are used in the treatment of urinary retention, glaucoma, smoking cessation, the diagnosis and treatment of myasthenia gravis, and the treatment of Alzheimer’s disease.
- Anticholinergics can be used in the treatment of bradycardias, bronchospasm, postoperative nausea and vomiting, bladder spasms, and diarrhea.
- Adrenoreceptor agonists/sympathomimetics include medications that are indicated for the treatment of hypertension, asthma (bronchodilators), and Parkinson’s disease. The drugs dobutamine, phenylephrine, and epinephrine are also in this category; they are used to treat hypotension, heart failure, cardiogenic shock, and anaphylaxis.
- Adrenoreceptor antagonists are indicated in the treatment of urinary retention (in benign prostatic hyperplasia), hypertension, dysrhythmias, angina, heart failure, and migraine prophylaxis.
It is important to remember that the four categories just discussed act as either an agonist or an antagonist for the receptors mentioned in Table 9.2.
Sympathetic Nervous System Stimulant and Blocker Characteristics
Medications that are classified as stimulants cover a wide range of drugs that increase the activity of the central nervous system (Farzam et al., 2023). Some of the medications in this category treat attention deficit hyperactivity disorder, narcolepsy, asthma, obesity, sinus congestions, and hypotension. Drugs in this category range from caffeine to amphetamines and from legal to illegal.
Since the sympathetic nervous system plays a rather large role in the regulation of the circulatory system and in the regulation of blood pressure, many medications that act to block the sympathetic nervous system reduce blood pressure (see Antihypertensive and Antianginal Drugs). Some of these drugs work by affecting the central nervous system, and others work at peripheral neuromuscular sites.
Parasympathetic Nervous System Stimulant and Blocker Characteristics
As mentioned earlier in this section, parasympathomimetic drugs mimic the physiologic effects of the parasympathetic nervous system by acting as the muscarinic acetylcholine receptors. Bethanechol, which treats urinary retention; carbachol, which is used in the treatment of open-angle glaucoma; and pilocarpine, which treats both open- and closed-angle glaucoma, are examples of direct-acting parasympathomimetic drugs. There are other indirect-acting parasympathomimetic drugs that cause an increase in the synaptic concentration of acetylcholine, which result in the extended stimulation of cholinergic receptors throughout both the CNS and PNS (Patel & Dewaswala, 2023).