Understanding Pharmacology:

A review of the most commonly acted upon receptors & transporter proteins

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The content provided in this Substack post is for entertainment and informational purposes only and is not intended to serve as medical advice. The views and opinions expressed herein are those of the writer and should not be taken as definitive or authoritative. Readers should not rely solely on the information provided in this post to make decisions about patient care. Instead, use this content as a starting point for further research and consult a qualified healthcare professional before making any changes to treatment or medication regimens.

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Below is a list of the 10 most commonly acted upon receptors and transporter proteins in psychiatry. Understanding the primary actions of each of these receptors will not only help you to understand how medications accomplish their goal, but it will also help you to understand some of the most common side effects that are experienced with the administration of various psychiatric medication.

1. H1 (Histamine 1 receptor): This receptor is found throughout the body, with roles in inflammation, allergic responses, and acting as a neurotransmitter in the brain. In the central nervous system, it's associated with the regulation of sleep, appetite, and cognitive processes. When blocked, as by some antipsychotics and antidepressants, it can cause sedation and increased appetite.

2. D2 (Dopamine 2 receptor): This is one of the five subtypes of dopamine receptors in the brain. It's linked to multiple psychiatric disorders including schizophrenia, ADHD, and substance use disorders. Dopamine is often referred to as the "reward" neurotransmitter because of its crucial role in pleasure and motivation. D2 receptor antagonists, such as some antipsychotic drugs, can help manage symptoms of schizophrenia and bipolar disorder.

3. 5-HT2 (Serotonin 2 receptor): This receptor is one of many in the serotonin system, and it's particularly relevant in mood regulation, anxiety, and schizophrenia. Drugs like selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotics work partly through action on these receptors. Blocking 5-HT2A receptors can alleviate symptoms of depression and anxiety, while blocking 5-HT2C receptors can lead to increased appetite and weight gain.

4. DAT (Dopamine Transporter): The dopamine transporter reabsorbs dopamine from the synapse back into the neuron, reducing its activity. Stimulants used in ADHD, like methylphenidate and amphetamines, block the DAT to increase the amount of available dopamine. This enhanced dopamine action improves attention and reduces impulsivity and hyperactivity.

5. SERT (Serotonin Transporter): This transporter is responsible for the reuptake of serotonin from the synapse back into the neuron. SSRIs block SERT, thereby increasing the amount of available serotonin. This has the effect of enhancing mood, reducing anxiety, and helping to regulate sleep cycles.

6. NMDA (N-Methyl-D-Aspartate) receptor: This glutamate receptor is involved in memory and learning, and it's also thought to be involved in the pathophysiology of depression and schizophrenia. Ketamine, an NMDA receptor antagonist, has been shown to have rapid-acting antidepressant effects.

7. GABA receptors: Gamma-Aminobutyric Acid (GABA) is the primary inhibitory neurotransmitter in the brain, responsible for reducing neuronal excitability. GABA receptors are a major target of anxiolytic medications such as benzodiazepines.

8. Mu-opioid receptor: This receptor is activated by endorphins, the body's natural "painkillers," as well as by opioid drugs. It is a target for pain management but is also implicated in addiction.

9. Alpha-2 adrenergic receptor: Located in the brain and peripheral nervous system, this receptor plays a role in regulating neurotransmitter release. Drugs that act on these receptors, like clonidine and guanfacine, are used to manage ADHD symptoms and certain anxiety disorders.

10. Cholinergic Receptors (Muscarinic and Nicotinic): These receptors respond to acetylcholine, a neurotransmitter essential for many functions in both the central and peripheral nervous system. In the brain, acetylcholine is involved in memory, mood, and overall cognitive function. There are two types of cholinergic receptors:

    • Muscarinic receptors: They are involved in the parasympathetic nervous system activities like heart rate, digestion, and salivation. In the brain, they contribute to learning and memory. Certain drugs that block these receptors, like anticholinergics, can cause side effects like dry mouth, constipation, and cognitive issues.

    • Nicotinic receptors: These are found in various locations including the nervous system, muscles, and adrenal glands. They are the target of nicotine, hence the name. In the brain, they influence cognitive functions. Nicotine's stimulatory and addictive properties are due to its action on these receptors.

In the future, we will share posts focusing in on each of these receptors in greater detail. We will also review various medications & focus on which receptors they are acting upon & the subsequent implications to keep in mind. “