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Proponents of the monoamine hypothesis argue that this lag is that the neurotransmitter activity enhancement is the result of auto receptor desensitization, which can take weeks. [59] Intensive investigation has failed to find convincing evidence of a primary dysfunction of a specific monoamine system in people with MDD.
The neurotrophic hypothesis of depression [1] proposes that major depressive disorder (MDD) is caused, at least partly, by impaired neurotrophic support.Neurotrophic factors (also known as neurotrophins) are a family of closely related proteins which regulate the survival, development, and function of neurons in both the central and peripheral nervous systems.
The pharmacology of antidepressants is not entirely clear.. The earliest and probably most widely accepted scientific theory of antidepressant action is the monoamine hypothesis (which can be traced back to the 1950s), which states that depression is due to an imbalance (most often a deficiency) of the monoamine neurotransmitters (namely serotonin, norepinephrine and dopamine). [1]
A monoamine reuptake inhibitor (MRI) [1] is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT).
Since their introduction in the late 1980s, second-generation antidepressants have largely replaced first-generation antidepressants, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), as the drugs of choice for the treatment of MDD due to their improved tolerability and safety profile.
After release into the synaptic cleft, monoamine neurotransmitter action is ended by reuptake into the presynaptic terminal. There, they can be repackaged into synaptic vesicles or degraded by the enzyme monoamine oxidase (MAO), which is a target of monoamine oxidase inhibitors, a class of antidepressants. [citation needed]
The original monoamine hypothesis postulates that depression is caused by a deficiency or imbalances in the monoamine neurotransmitters (5-HT, NE, and DA). This has been the central topic of depression research for approximately the last 50 years; [ 12 ] [ 198 ] it has since evolved into the notion that depression arises through alterations in ...
The monoamine hypothesis was originally proposed based on observations that reserpine, a drug which depletes the monoamine neurotransmitters, produced depressive effects in people, [201] and that certain hydrazine antituberculosis agents like iproniazid, which prevent the breakdown of monoamine neurotransmitters, produced apparent ...