Drug Interactions on Synapse

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Mammalian Physiology

Homework on Drug Mechanisms
1. Release and degradation of the neurotransmitter inside the axon terminal. Drug: Reserpine
Pharmacology: Most often used to treat mild to moderate hypertension. Mode of action: Reserpine inhibits the ATP/MG2+ pump responsible for packaging neurotransmitters into vesicles in the presynaptic neuron. This causes the free neurotransmitters to be degraded by MAO, leading to a reduction in catecholamines.

2. Increased neurotransmitter release into the synapse.
Drug: Black Widow Venom
Pharmacology: Neurotoxin.
Mode of action: Alpha-latrotoxin (a-LTX) is the three-dimensional protein toxin unique to widow spiders. This protein has a high affinity for receptors that are specific for neuronal and endocrine cells of vertebrates. a-LTX will assemble into homotetrameric complexes which embed in the plasma membrane of the presynaptic synapse. a-LTX will then bind to a receptor on the plasma membrane and form cation-permeable channels (specifically Ca 2+, although Na +, K +, Mg 2+, etc. can enter the membrane too), allowing a massive influx of Ca 2+ into the axon terminal and cause massive release of any and all neurotransmitter in the terminal. A swollen terminal bouton is left in its wake.

3. Prevention of neurotransmitter release into the synapse.
Drug: Reserpine.
Pharmacology: Most often used to treat mild to moderate hypertension. Rarely used as an antipsychotic. Mode of action: Reserpine works by irreversibly blocking the vesicular monoamine transporter (VMAT). This transporter normally transports dopamine (DA), 5-HT (serotonin), and norepinephrine (NE) from the cytoplasm to the vesicle in the presynaptic neuron. Because these neurotransmitters are not packaged, they are degraded quickly by monoamine oxidases (MAOs).

4. Inhibition of synthesis of the neurotransmitter.
Drug: p-chlorophenylalanine (PCPA)
Pharmacology: Indirect serotonin antagonist. Primarily used in research. Mode of action: PCPA acts...
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