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Effects of antidepressants on uptake and receptor systems in the brain.

Abstract

Many antidepressant drugs inhibit the neuronal uptake of norepinephrine, serotonin, epinephrine and/or dopamine. Some newer antidepressant drugs are highly selective in their ability to inhibit the uptake of one or more of these monoamines. This uptake inhibition, which would be expected to increase the synaptic concentrations of the neurotransmitter initially, has traditionally been thought to be the mechanism of antidepressive action of these drugs. Some drugs, which are not uptake inhibitors, may block presynaptic alpha 2 receptors to enhance norepinephrine release, leading by a different mechanism to increased synaptic concentrations of norepinephrine. Adaptive changes in neurotransmitter receptors occur after chronic treatment of laboratory animals with these drugs, and these changes may be important components of the overall mechanism of antidepressant efficacy. Presently, evidence that these adaptive changes occur in humans is limited, and the significance of the changes to the treatment of depression is unknown. Some antidepressant drugs also have high affinity for neurotransmitter receptors, and direct antagonism of these receptors is the basis for some of their side effects, e.g., anticholinergic side effects that are prevalent with the tricyclic drugs.

PMID:
2868490
[Indexed for MEDLINE]
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