Iloperidone, Approved For Treatment Of Schizophrenia

The new drug is called iloperidone; the brand name in the USA
will be Fanapt.  It is yet another antipsychotic that
blocks D2 and 5HT2 receptors.  Although there is no universally
accepted way of classifying drugs into families, it will be referred to
as an atypical or second-generation
antipsychotic.  This designation will indicate a loose kind of
similarity to risperidone, aripiperazole, ziprasidone, quetiapine,
olanzapine, clozapine, and paliperidone. 



It turns out that there is a Wikipedia page for href="http://en.wikipedia.org/wiki/Iloperidone">iloperidone. 
It is not one of the better pages on Wikipedia. 

Iloperidone is a monoamine directed towards acting upon and
antagonizing specific neurotransmitters.

Iloperidone does act upon the transmitter.  It blocks the
receptor, which causes the transmitter to be ineffective, or less
effective, at transmitting whatever message it otherwise would have
transmitted.



There are several other quibbles I have with the Wikipedia page. 
If I were unemployed, I would edit it.  But it is going to take a
lot of work.



Anyway, I could write the kind of blog post that I usually have written
when potentially-interesting new drugs come out.  But it turns out
that there is already a good, concise article in an open-access
journal.  It says all the things I would have said. 

href="http://www.currentpsychiatry.com/article_pages.asp?AID=7838">Iloperidone
for schizophrenia

Peter J. Weiden, MD,  and Jeffrey R. Bishop, PharmD, BCPP

Current Psychiatry Online

Vol. 8, No. 9 / September 2009

Iloperidone is a second-generation (atypical) antipsychotic
the FDA approved in May 2009 for treating acute schizophrenia in adults
(Table 1). Iloperidone is not a derivative (metabolite, isomer, or
different formulation) of any other antipsychotic. Clinical trials have
shown that iloperidone is efficacious and suggest that for some
patients its side-effect profile may be more favorable than that of
other antipsychotics.

It is expected to be available later this year.  It is not
possible for me, or anyone else, to say exactly when this will be.



The high points are: oral bioavailability 95%, half-life about 18
hours, protein binding about 95%, high affinity for D2 and 5HT2A, low
for H1, minimal for muscarinic, and moderate for NEα1.  The cost
will be too high, but I don't know exactly how high.  The
manufacturer, Vanda Pharmaceuticals, reportedly is working on a
long-acting injectable product.



The one sort of interesting thing has to do with the alpha-1
antagonism.  This is a nuisance sometimes, because it can cause
orthostatic hypotension (dizziness upon standing up, due to drop in
blood pressure).   This is a side effect, which may or may
not happen in a given individual.  It is potentially an adverse
effect. 



Prazosin is an antihypertensive drug that blocks alpha-1
receptors.  Prazosin has been used, off-label, to href="http://ajp.psychiatryonline.org/cgi/content/abstract/160/2/371">reduce
nightmares in persons with PTSD. 



Could iloperidone have a similar effect?  If so, it would be a
side effect, but not an adverse effect.  It would be a beneficial
side effect.  It remains to be seen whether this will turn out to
be the case.  In general, it is tricky to anticipate clinical
effects, based upon the in vitro pharmacology of a drug, when it
comes to the effects in the brain.