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→Mechanism of Action
Together the LC and Raphe nuclei form parts of the ascending reticular activating system that has projections throughout the CNS and are involved in mood, wakefulness, sleep cycles and arousal as well as pain modulation and a host of other maintenance functions such as meal patterning.
Together the LC and Raphe nuclei form parts of the ascending reticular activating system that has projections throughout the CNS and are involved in mood, wakefulness, sleep cycles and arousal as well as pain modulation and a host of other maintenance functions such as meal patterning.
The effect on neurotransmitter levels is quite rapid, but therapeutic effects take 3 weeks or more to become apparent. This is because although clomipramine and many other antidepressants (SRI, SSRI, TCA, atypical) have immediate effects on synaptic neurotransmission, the lasting corrections in mood are the result of intracellular changes and in receptor numbers. This is dependent on secondary messenger systems (cAMP, Ca<sup>2+</sup>, cGMP, IP<sub>3</sub>3), gene expression and protein synthesis that take time to occur. Receptors for nor-adrenaline and serotonin are linked to metabotropic G-proteins that can induce changes in protein synthesis such as the up- and down-regulation of receptors. There are 14 known classes of 5-HT receptors, of these, in anxiety problems the 5-HT<sub>1</sub> receptor is the most relevant.
The effect on neurotransmitter levels is quite rapid, but therapeutic effects take 3 weeks or more to become apparent. This is because although clomipramine and many other antidepressants (SRI, SSRI, TCA, atypical) have immediate effects on synaptic neurotransmission, the lasting corrections in mood are the result of intracellular changes and in receptor numbers. This is dependent on secondary messenger systems (cAMP, Ca<sup>2+</sup>, cGMP, IP<sub>3</sub>), gene expression and protein synthesis that take time to occur. Receptors for nor-adrenaline and serotonin are linked to metabotropic G-proteins that can induce changes in protein synthesis such as the up- and down-regulation of receptors. There are 14 known classes of 5-HT receptors, of these, in anxiety problems the 5-HT<sub>1</sub> receptor is the most relevant.
For example, in states of anxiety and depression the following presynaptic changes are thought to occur:
For example, in states of anxiety and depression the following presynaptic changes are thought to occur: