NEW YORK, Jun 24, 2002 /PRNewswire-FirstCall via COMTEX/ -- Forest
Laboratories, Inc. (NYSE: FRX) announced today the results of a pre-clinical
study that may provide a potential explanation why the investigational selective
serotonin reuptake inhibitor (SSRI) Lexapro(TM) (escitalopram oxalate) has been
shown in clinical trials to be more than twice as potent as the widely
prescribed antidepressant Celexa(TM) (citalopram HBr). The microdialysis study
results were presented at the 23rd Collegium Internationale
Neuro-Psychopharmacologium (CINP) Congress in Montreal. Lexapro is the
single-active isomer of Celexa, a racemic mixture with two mirror-image halves
called the S- and R-enantiomers.
The new study shows that Lexapro (the S-enantiomer of citalopram), when given at
2 mg/kg subcutaneously (s.c.), was more than twice as potent as Celexa at 4
mg/kg s.c. (2.0 mg/kg S-enantiomer + 2.0 mg/kg R-enantiomer) in increasing brain
serotonin levels (about 300 percent vs. 200 percent, respectively). In contrast
to Lexapro, the R-enantiomer of citalopram, when given at 2.5 mg/kg s.c., did
not increase brain serotonin levels.
"The results suggest that the R-enantiomer, when given as part of racemic
Celexa, decreases the ability of the S-enantiomer to increase serotonin levels
in the brain," said Jack Gorman, M.D., Lieber Professor and Vice Chair for
Research at the College of Physicians and Surgeons, Columbia University. "This
is significant because the data demonstrate that Lexapro when given alone is
more than twice as potent as when an equal amount of the S-enantiomer is given
in combination with the same amount of the R-enantiomer, as is the case for
Celexa."
The mechanism by which the R-enantiomer affects the ability of the S-enantiomer
to increase brain serotonin levels is still unknown. It is possible that the
R-enantiomer might interfere with the well-known feedback inhibition seen in the
serotonin system.
About the Microdialysis Technique
The microdialysis technique allows sampling of small quantities of biological
fluids from discrete, closed compartments in the body, such as the brain. The
samples can then be subjected to analysis for the determination of
concentrations of various drugs, chemicals and/or neurotransmitters. A major
advantage of the technique is that it can be performed in the conscious animal.
The procedure involves implantation of a microdialysis probe in the desired
specific location, in this case the frontal cortex of rat brain. An added
advantage of this technique is that it also permits application of drugs through
the microdialysis probe to the area of interest. Thus, one can determine how a
particular drug or treatment changes the neurochemistry in a particular brain
region without the interference/modulation of the other brain regions or
pharmacokinetic considerations.
About Forest Laboratories and Its Products
Forest Laboratories develops, manufactures, and sells ethical pharmaceutical
products that are used for the treatment of a wide range of illnesses. Forest's
growing line of products includes: Celexa, which has been prescribed for more
than eight million U.S. patients and is the fastest growing antidepressant in
the U.S.; Tiazac(R), a once-daily diltiazem, which is indicated for the
treatment of angina and hypertension; and Aerobid(R) an inhaled steroid
indicated for the treatment of asthma. The Company has also entered into a
co-promotion agreement with Sankyo of Japan for the marketing of Benicar(TM)
(olmesartan medoxomil)* for the treatment of hypertension.
* Benicar is a registered trademark of Sankyo Pharma.
Except for the historical information contained herein, this release contains
forward-looking statements that involve a number of risks and uncertainties,
including the difficulty of predicting FDA approvals, acceptance and demand for
new pharmaceutical products, the impact of competitive products and pricing, the
timely development and launch of new products, and the risk factors listed from
time to time in the Company's SEC reports, including the Company's Annual Report
on Form 10-K for the fiscal year ended March 31, 2001, and the quarterly report
on Form 10-Q for the periods ended June 30, 2001, September 30, 2001, and
December 21, 2001.