Posted by Thomas123 on February 24, 2003, at 0:07:42
In reply to Re: Abilify produces sedation at low dosages only?, posted by SLS on February 23, 2003, at 22:13:46
The prescribing information for Abilify states somnolence is the only side-effect which is dose related. It is about 8.5% for 15 milligrams, 7.5 percent for 20 milligrams and 15% for 30 milligrams. See www.abilfiy.com. I was unable to cut and paste from the PDF.
Your post says for neuroleptics side-effects aren't dosage related. This is false. EPS go up with typical neuroleptics when dosage is increased. Atypical neuroleptics have many actions. Increase dosage and side-effects will go up with them. Sleepiness comes from antihistaminergic and anticholigneric actions as much as from blockade of dopamine receptors. Haldol is a very powerful dopamine antagonist but lacks sedative properties because it is only a dopamine antagonist. Even if Clozaril and Seroquel are only transiently on the receptor if there is a lot of Clozaril or Seroquel in the system there will be a new neurolpetic molecule around to pop on the receptor when the old one pops off.
These boards have talked about a sleepiness associated with Abilify but the fact remains this is an uncommon side-effect for Abilfiy according to the published studies.
Abilfy isn't transiently on the receptor. It has a very low dissociation constant. It is on for a long time. It is third generation drug. Increase the dosage enough and it will totally displace dopamine from the receptor and there will be a decreased agonization of dopamine receptors given that Abilify is a weaker agonist than dopamine.
Low dosages by agonizing presynatpic receptors weakly increase the release of dopamine from terminals relative to the agonization of dopaminergic autoreceptors by dopamine and thereby have a stimulatory affect.
There is really no angle in trying to tease out a differential effect between pre and post synaptic dopamine receptors as presynaptic receptors are D2 receptors and the same kind of receptor which must be blocked to obtain an antipsychotic effect. One has to look at net effects.
Best of luck, of course.
poster:Thomas123
thread:203168
URL: http://www.dr-bob.org/babble/20030219/msgs/203243.html