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Chapter: Biochemical Pharmacology : Drugs that act on sodium and potassium channels

Mechanisms of drug action on synapses

Drugs may influence synaptic transmission by different mechanisms:

Mechanisms of drug action on synapses

 

Drugs may influence synaptic transmission by different mechanisms:

 

1.  Direct agonists and antagonists will directly bind to the postsynaptic receptor and either activate or competitive-ly block it.

 

2.  In many synapses, there are both post- and presynaptic receptors for the transmitter. The transmitter will act in an inhibitory fashion at the presynaptic membrane, thus providing for feedback control of release (Figure 7.4a). If its action is excitatory at the postsynaptic membrane, it is easy to see that the two receptors should be differ-ent. In this case, drugs may be developed that act solely on the presynaptic receptor. Such presynaptic agonists will then reduce the amount of transmitter available at the postsynaptic membrane, whereas presynaptic antag-onists will increase it.

 

3.  Drugs may augment the effect of the endogenous neuro-transmitter by inhibiting its usually very rapid elimina-tion from the synaptic cleft by either enzymatic degra-dation or presynaptic reuptake (Figure 7.4b). Enzymatic degradation occurs with acetylcholine, whereas presy-naptic reuptake is used to scavenge most other small transmitter molecules.

 

4.  Within the presynaptic neuron, synthesis, breakdown, or vesicular accumulation of the transmitters may be al-tered. This may lead to short-term release and long-term depletion of neurotransmitter. These mechanisms are relevant to cocaine and mechanistically similar drugs of abuse. Drugs that act according to any of these mecha-nisms are usually referred to as indirect agonists or an-tagonists, respectively.

 

We will see examples of all of these mechanisms in subse-quent chapters.


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