Reposting an abstract, but followed by an AP story from yesterday. Could one of the neuro types comment on the juxtaposition, please? Harry?
Thanks!
J Pharmacol Exp Ther 1999 Feb;288(2):590-6
Atypical neuroleptics enhance histamine turnover in brain via
5-Hydroxytryptamine2A receptor blockade.
Morisset S, Sahm UG, Traiffort E, Tardivel-Lacombe J, Arrang JM, Schwartz J
Unite de Neurobiologie et Pharmacologie Moleculaire (U.109) de Institut National de la
Sante et de la Recherche
Medicale,
Paris, France.
[Medline record in process]
Clozapine and olanzapine behave as weak H3-receptor antagonists in vitro with Ki
values around 1 and 50
&mgr;M,
respectively. Despite these modest apparent affinities, both compounds given orally to
mice, nearly doubled
steady-state
tele-methylhistamine levels in brain, with ED50 values as low as 1 and 3 mg/kg,
respectively, an effect comparable
to those of
potent H3-receptor antagonists. This effect corresponded to an enhancement of
histamine turnover rate from 45 to
73 ng/g/h as
measured in the case of olanzapine using the pargyline test. Other antipsychotics
displaying, such as clozapine and
olanzapine,
high 5-hydroxytryptamine (5-HT)2A receptor antagonist potency, i.e., risperidone,
thioridazine, seroquel, and
iloperidone, also
enhanced markedly tele-methylhistamine levels. This effect was 1) additive with that of a
pure H3-receptor
antagonist,
ciproxifan, 2) mimicked by a 5-HT2A receptor antagonist, ketanserin, 3) reversed by a
5-HT2A receptor agonist,
DOI, 4) not
shared by antipsychotics with low affinity for the 5-HT2A receptor, i.e., haloperidol,
sulpiride, raclopride, or
remoxipride that,
on the contrary, tended to reduce tele-methylhistamine levels. We conclude that in
contrast to "typical"
antipsychotics, "atypical"
antipsychotics stimulate histamine neuron activity via blockade of the 5-HT2A receptor
in vivo. This effect does
not appear to
account for their reduced extrapyramidal side-effects but may underlie their
pro-cognitive properties.
01:07 AM ET 03/11/99
Study: Drug Gives Parkinson's Relief
Study: Drug Gives Parkinson's Relief
By The Associated Press=
Low doses of an anti-schizophrenia drug can relieve psychotic
symptoms in patients with Parkinson's without worsening the tremors
or other physical signs of the disease, researchers reported today.
More than 1 million Americans have Parkinson's, a neurological
disorder that causes progressive rigidity, tremors and difficulty
moving. There is no cure, but drugs can slow the progress of the
disease and ease symptoms.
However, up to one-fifth of Parkinson's sufferers develop
hallucinations, delusions and other psychotic symptoms from the
drugs used to treat the disease. And most anti-psychotic drugs just
make the tremors and jerky movements worse.
Until recently, doctors had few options, and drug-induced
psychosis is the chief reason Parkinson's patients are put in
nursing homes.
However, a study in today's New England Journal of Medicine
found that the anti-psychotic drug clozapine decreased the
psychotic symptoms and the tremors, and did not worsen other
symptoms.
Doses of 6 to 50 milligrams _ a fraction of the amount used to
treat schizophrenia _ helped the patients. At higher doses,
clozapine can lead to a fatal blood disorder. Even at low doses,
patients must be carefully monitored.
The study was led by Dr. Joseph Friedman of Brown University and
Memorial Hospital of Rhode Island. |
