Posted by SLS on February 23, 2003, at 20:12:42
Hi.
Will raising the dosage of Abilify get rid of the sedation some people experience when initiating treatment with low dosages?
I recently started Abilify. My doctor started me off at 20mg. He said that we might as well start this high because, in his experience, the intensity of side-effects produced by neuroleptics is nearly the same at high dosages as low dosages. I have been at this dosage for over a week. The only side-effects I have thus far experienced are mild to moderate insomnia, slightly blunted cognition, mild headache, and perhaps dry mouth. They are at worst minor annoyances that seem to be dissipating.I have begun to think that for those people whom experience sedation, their dosage of Abilify might be too low. Abilify acts as an agonist (stimulator) of presynaptic dopamine DA2 autoreceptors. These presynaptic receptors tend to attract and bind dopamine, along with various drugs, significantly more strongly than do postsynaptic receptors. When stimulated, these autoreceptors instruct the neuron to reduce it's rate of synthesis and release of dopamine. This usually results in sedation or somnolence.
The best example of the presynaptic DA agonist sedation phenomenon is the drug, apomorphine. Apomorphine is a non-selective DA agonist that produces arousal, excitement, and amphetamine-like stereotypical behavior at moderate and higher dosages. However, at low dosages, it produces profound sedation due to its preferential stimulation of presynaptic autoreceptors.
I feel that these facts yield a hypothesis: Raising the dosage of Abilify will abolish the sedation experienced by some people at low dosages.
For some people, Abilify produces sedation at low dosages in a manner similar to apomorphine due to preferential presynaptic DA receptor agonism. This sedation is perhaps amplified by the ability of Abilify to act as a postsynaptic antagonist in the presence of dopamine. Perhaps raising the dosage beyond a certain threshold would change the balance between presynaptic and postsynaptic stimulation in favor of the latter to mitigate or abolish sedation. It is possible, however, that the synaptic dynamics of some individuals prevent this net reversal from occurring.
I will stop this post here so I that I can watch Bruce perform on the Grammys.
Bye...
- Scott
poster:SLS
thread:203168
URL: http://www.dr-bob.org/babble/20030219/msgs/203168.html