Changes

#Central and peripheral anticholinergic action

#Central and peripheral anticholinergic action

#Presynaptic blocking of CNS biogenic amines such as noradrenaline and serotonin (5-HT) and therefore their potentiation <ref name="Overall1">Overall, K.L., 2004. Paradigms for pharmacologic use as a treatment component in feline behavioral medicine. Journal of Feline Medicine and Surgery 6, 29-42.</ref>.

#Presynaptic blocking of CNS biogenic amines such as noradrenaline and serotonin (5-HT) and therefore their potentiation <ref name="Overall1">Overall, K.L., 2004. Paradigms for pharmacologic use as a treatment component in feline behavioral medicine. Journal of Feline Medicine and Surgery 6, 29-42.</ref>.

Clomipramine blocks the reuptake of serotonin and nor-adrenaline from the synaptic cleft, thus causing a build up of these neurotransmitters in the synapse.

Clomipramine blocks the reuptake of serotonin and nor-adrenaline from the synaptic cleft, thus causing a build up of these neurotransmitters in the synapse.

The effect of clomipramine is to elevate mood, reduce anxiety and block the development of panic.

The effect of clomipramine is to elevate mood, reduce anxiety and block the development of panic reactions.

The main target of action for these drugs are structures in the brain that depend upon nor-adrenaline and serotonin as major neurotransmitters:

The main target of action for these drugs are structures in the brain that depend upon nor-adrenaline and serotonin as major neurotransmitters, including:

:*Noradrenaline: Locus Coeruleus (LC)

:*Noradrenaline: Locus Coeruleus (LC)

:*Serotonin: Raphe nuclei

:*Serotonin: Raphe nuclei

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 is 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, selective serotonin reuptake inhibitor (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, Ca²⁺, cGMP, IP₃), 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-HT₁ 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 serotonergic antidepressants (SRI, selective serotonin reuptake inhibitor (SSRI), TCA, atypical) have immediate effects on synaptic neurotransmission, the lasting changes in emotional response are the result of intracellular changes and in receptor numbers. This is dependent on secondary messenger systems (cAMP, Ca²⁺, cGMP, IP₃), 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-HT₁ 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: