14 Drug and Toxin Effects

Drugs and toxins can alter neuron functioning in a range of ways, from activation to inhibition and all levels of modulation. Although many drugs exist that alter molecular process typical of many cells, this lesson will focus on neuron-specific targets.

Synaptic Effects

As we have seen, the synapse is an incredibly complex structure, and for small molecule neurotransmitters, the entire “lifecycle” of the transmitter occurs in this space – synthesis, packaging, release, action, and termination. This means there are numerous targets upon which drugs and toxins can act and alter synaptic communication.

Drug Effects on Neurotransmitter Release

Drugs can alter neurotransmitter synthesis pathways, either increasing or decreasing the amount of neurotransmitter made in the terminal, affecting how much transmitter is released. An example of this is administration of L-DOPA, a dopamine precursor molecule that results in increased dopamine production; it is used as a treatment for Parkinson’s Disease.

Neurotransmitter packaging is another site of possible drug action. Reserpine, which has been used to treat high blood pressure, blocks the transport of the monoamine transmitters into vesicles by inhibiting the vesicular monoamine transporter (VMAT). This decrease the amount of neurotransmitter stores and the amount of neurotransmitter released in response to an action potential.

Illustration of synaptic terminal showing drug action on transmitter synthesis and packaging. Details in caption.
Figure 14.1. Drugs and toxins can alter neurotransmitter synthesis and packaging into synaptic vesicles. L-DOPA increases the synthesis of dopamine in the terminal. Reserpine prevents packaging of the biogenic amines, resulting in low concentrations of transmitter stored in synaptic vesicles. ‘Drug Effects on Neurotransmitter Release’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC BY-NC-SA) 4.0 International License.

Drug Effects on the Postsynaptic Membrane

The neurotransmitter receptors are another critical location for drug and toxin action. Agonists mimic neurotransmitter effects, whereas antagonists block neurotransmitter effects. Muscimol, a component of some mushrooms, is an agonist for the ionotropic GABA receptor. Bicuculine, a component of some plants, is an antagonist to this receptor and blocks the action of GABA. Additionally, many chemicals are able to modulate receptors in either a positive or negative fashion. Alcohol binds to the GABA receptor and increases the time the receptor is open when GABA binds.

Illustration of synaptic terminal showing drug action on postsynaptic receptors. Details in caption.
Figure 14.2. Drugs and toxins can alter neurotransmitter receptors on the postsynaptic neuron. A GABA agonist, muscimol, would replicate the actions of GABA and cause an IPSP. A GABA antagonist, bicuculine, would prevent GABA actions resulting in no IPSP. Modulators such as alcohol, alter how the receptor works, so when GABA binds the response is a stronger IPSP than when alcohol is not present. ‘Postsynaptic Drug Effects’ by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC BY-NC-SA) 4.0 International License.

Drug Effects on Neurotransmitter Clearance

Finally, neurotransmitter degradation and reuptake can also be altered by drugs and toxins. Depending on the neurotransmitter, enzymes located in either the synapse or in the terminal are responsible for degradation of the transmitter, and these enzyme can be blocked by drugs. Organophosphates are found in many pesticides and prevent the action of acetylcholinesterase, the enzyme that breaks down acetylcholine in the synapse. This inhibition increases acetylcholine action on the postsynaptic neuron. Monoamine oxidase inhibitors (MAOIs) prevent monoamine oxidase from degrading the biogenic amine neurotransmitters. MAOIs have been used as antidepressants since they increase the amount of transmitter available. Additionally, drugs can prevent the reuptake of neurotransmitters into the presynaptic terminal. Cocaine blocks the dopamine transporter, which results in increased action of dopamine in the synapse.

Illustration of synaptic terminal showing drug action on transmitter clearance. Details in caption.
Figure 14.3. Drugs and toxins can alter neurotransmitter degradation and reuptake into the presynaptic terminal. Organophosphates prevent the degradation of acetylcholine in the synapse. MAOIs prevent the degradation of monoamine transmitters in the terminal. Cocaine prevents dopamine from being transported into the presynaptic terminal. All of these effects lead to increased neurotransmitter action and availability. ‘Drug Effects on Neurotransmitter Clearance” by Casey Henley is licensed under a Creative Commons Attribution Non-Commercial Share-Alike (CC BY-NC-SA) 4.0 International License.

Non-Synaptic Effects

Drugs and toxins can also affect neuron function by acting outside of the synapse. For example, some chemicals change voltage-gated ion channel dynamics. Veratridine, a compound found in plants from the lily family, prevents voltage-gated sodium channels from inactivating. Initially, this causes an increase in neurotransmitter release, but it can quickly lead to excitotoxicity.

Key Takeaways

  • There are many ways in which drugs and toxins can alter neuron function
  • Effects can be excitatory, inhibitory, or modulatory

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