Neuropharmacology: How do your drugs work?

Almost everyone uses medications at some point in their life, but what are they actually doing in the nervous system? Neuropharmacology is a branch of medical science dealing with the properties and actions of a drug on and in the nervous system. Drugs are grouped into one of the following based on how they work: neurotransmitter substrates, reuptake inhibition, receptor modification, and enzyme modulation (Figure 1).

Figure 1. Drugs can be classified into one of the following based on their mechanism of action: reuptake inhibition (1), receptor modification (2), neurotransmitter substrates (3), or enzyme modification.

Figure 1. Drugs can be classified into one of the following based on their mechanism of action: reuptake inhibition (1), receptor modification (2), neurotransmitter substrates (3), or enzyme modification.

Neurotransmitter substrates

Neurotransmitter substrates are amino acids that act as precursors for neurotransmitter synthesis. Neurotransmitter substrates, such as the drug Levodopa, will affect the amount of neurotransmitters available.

Reuptake inhibition

Reuptake inhibition is the prevention of neurotransmitter transport from the synapse back into the neuron that released it. This increases neurotransmitter levels outside the cells. These substances are commonly referred to as reuptake inhibitors. Examples of reuptake inhibitors include selective serotonin reuptake inhibitors (SSRI) like citalopram or fluoxetine, serotonin and norepinephrine reuptake inhibitors (SNRI) like venlafaxine and duloxetine, and norepinephrine and dopamine reuptake inhibitors (NDRI) like bupropion.

Receptor modification

Neuronal receptor modification includes the mimicry, enhancement, or blocking of neurotransmitter binding to its receptor. Therapeutic agents in this category include receptor agonists and receptor antagonists.

Receptor agonists can either act like or enhance the action of neurotransmitters. Mimics bind to a specific neurotransmitter receptor and cause a similar action. Agents that enhance the action of neurotransmitters bind to the neurotransmitter receptor along with the neurotransmitter. This amplifies the effect of the neurotransmitter. Clonazepam, diazepam, and zolpidem are all classified as receptor agonists.

Receptor antagonists have the opposite effect of agonists. They bind to neurotransmitter receptors, blocking the neurotransmitter from activating the receptor. This decreases neurotransmission. One common example of a receptor antagonist is diphenhydramine, which is commonly used to treat allergies. It is a histamine receptor antagonist. It reduces the symptoms of allergies by blocking peripheral histamine receptors. Diphenhydramine also blocks central histamine receptors that are involved in wakefulness. When it blocks receptors in the central nervous system, the drowsiness often felt with the use of this drug can occur.

Enzyme modulation

Enzyme modulators alter the activity of an enzyme. Some enzymes break neurotransmitters down into their inactive metabolites. Pharmaceutical enzyme inhibitors can slow the breakdown of neurotransmitters, leaving more neurotransmitters to transmit signals. Examples are monoamine oxidase inhibitors (MAOI) such as selegiline or phenelzine or acetylcholinesterase inhibitors (AChEI) such as carbamates.

Many pharmaceuticals affect the nervous system by altering the levels or activity of neurotransmitters. Identifying which neurotransmitters are out of balance will help to determine the appropriate therapy to improve patient outcomes. For more information on which neurotransmitters are affected by different pharmaceuticals, please see the Prescribing Information for Select Drugs reference document.

Muller, W.E., et al. (1998) Pharmcopsych. 31:16-21.
Turner, E.H., et al. (2006) Pharmcol Ther. 109:325-338.
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