Precise mechanism of antidepressant activity of<unk> s remains somewhat uncertain, but a number of biochemical functions associated with<unk>  treatment have been established.<unk> s primarily inhibit SERT in the brain and have negligible effects on DAT and NET. The<unk> s also have less affinity for α1, α2, H1 and muscarinic receptors, which might explain the differences of adverse events between TCAs and<unk> s. Although<unk> s arrive rapidly to the brain after administration and the effects on 5-HT re-uptake can be measured instantly, it takes about 2–4 weeks to get therapeutic effects. The<unk> s have very high and selective affinity for SERT and after administration they inhibit SERT immediately. SERT inhibition is implicated in the antidepressant activity of<unk> s. 70-80% inhibition of SERT is usually necessary to induce antidepressant effects and higher dosage does not induce greater antidepressant effects for average patients. Higher dosage does, however, increase the incidence and severity of adverse events associated with excessive 5-HT re-uptake inhibition. Figure 2 Inhibition of re-uptake transport proteins, e.g. SERT, results in increased concentration of neurotransmitters, e.g. 5-HT, in the synaptic cleft, leading to improvement of depression symptoms<unk> s prevent 5-HT from binding to SERT which prevents absorption of 5-HT back into the presynapse terminal, where it is metabolized by monoamine oxidase or stored in secretory vesicles. As a result, the 5-HT concentration increases at the somatodendritic area of the 5-HT neuron but not so much at the axon terminal area (demonstrated in figure 2). This increase in 5-HT concentration causes desensitization of somatodendritic 5-HT1A autoreceptors. When these 5-HT1A autoreceptors have been downregulated, they will no longer restrict the impulse flow of the 5-HT neuron. The impulse flow is turned on and as a result 5-HT is released at the axon terminal. However, this increase of 5-HT does not happen quickly compared to the increase of 5-HT at the somatodendritic area of the 5-HT neuron. This delay is caused by the time it takes 5-HT to downregulate 5-HT1A autoreceptors and turn on the neuro impulse flow of the 5-HT neuron. This delay can explain the reason why antidepressants do not have effect on depression immediately. This can also be the reason why the antidepressant mechanisms can be connected to the increasing neuro impulse flow from 5-HT neurons, where as the concentration of 5-HT increases at the axon terminal before<unk> s start to work properly. When<unk> s have (1) inhibited the re-uptake pump, (2) increased somatodendritic 5-HT, (3) desensitized somatodendritic 5-HT1A autoreceptors, (4) turned on the impulse flow and (5) increased the release of 5-HT from axon terminal, the last step might be desensitization of postsynaptic 5-HT receptors. This desensitization could be the reason for reduction of adverse effects of<unk> s as tolerance develops.
Development and discovery of SSRI drugs
Suicide prevention
Recovered-memory therapy
Chronic fatigue syndrome treatment
Drug rehabilitation
Alternative therapies for developmental and learning disabilities
Experimental cancer treatment
Alternative cancer treatments