Posted by SLS on August 21, 2000, at 15:50:39
In reply to Translation please, SLS, posted by dj on August 21, 2000, at 10:39:28
> > I believe this new preparation consists of one of the fluoxetine stereoisomers rather than a racemate.
> ???? huh ????
I'm rusty and dusty, so I hope someone will jump in and correct me:Organic molecules often have variations in the arrangement of their atoms. Two molecules that have the same combination of atoms but that are arranged differently are called "isomers". If the differences between these molecules involve the placements of several attachments to a single hub atom three-dimensionally (chiral center), they are called stereoisomers or enantiomers. These two arrangements are mirror-images of each other. One will cause polarized light to rotate to the right (dextro-rotatory e.g. d-amphetamine); the other will rotate it to the left (levo-rotatory e.g. l-amphetamine). Not only do these two molecules rotate light differently, but they can also act differently chemically and pharmacologically.
Dexedrine (d-amphetamine, dextroamphetamine), is a drug preparation containing only one of the enantiomers of amphetamine. Adderal is a preparation containing both l- and d- isomers. A preparation in which the two enantiomers remain combined is described as being racemic, or is said to be a racemate. (A racemic mixture will not rotate polarized light). In addition to the direction in which they rotate light, enantiomers are also differentiated from each other by describing the relative order in which the atoms appear around the chiral center (R and S).
Prozac is a preparation containing fluoxetine racemate. It contains both R and S enantiomer molecules. It is hoped that one of the isomers (R) will produce less side effects while retaining its therapeutic efficacy.
I think my doctor, Jeffrey T. Apter, M.D., may be investigating isomers of various psychiatric drugs. Anyone interested may want to look into his clinical studies.New Jersey:
Princeton Biomedical Research
1-800-BIOMED7
1-800-246-6337http://members.aol.com/jtapter/index.html
- Scott
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Regarding R-fluoxetine (improved Prozac):
From
Clinical Psychiatry News
Fluoxetine Isomer May Hold Advantages Over Prozac
Elizabeth Mechcatie, Senior Writer
[Clinical Psychiatry News 27(3):7, 1999. © 1999 International Medical News Group.]Researchers are hoping that an isomer of the fluoxetine molecule may offer clinical advantages over Prozac.
A shorter half-life and effects on a cytochrome P-450 enzyme by the isomer may reduce the risk of drug interactions. Whether these potential benefits will translate to human benefits will be determined in clinical trials, which have just begun.
Fluoxetine is an enantiomer, a compound with two mirror-image forms --
S-fluoxetine and R-fluoxetine. Researchers have isolated R-fluoxetine, which is now being tested in healthy volunteers in the first phase of clinical trials.
Both the "S" and the "R" isomers of the fluoxetine molecule are active in the currently available selective serotonin reuptake inhibitor, but the "R" portion alone is being pursued as a therapeutic entity because it has a shorter half-life than fluoxetine and it appears to have less of a propensity to inhibit the P4502D6 isoenzyme, said Dr. Mark Demitrack, director of clinical development at Eli Lilly Research Labs in Indianapolis.
The latter feature has the potential to reduce the risk of drug-drug interactions with agents that are metabolized by this isoenzyme, such as the tricyclics, he said in an interview.
This year, the company expects to begin phase II clinical trials of R-fluoxetine in patients with major depression and hopes to complete phase III trials and file for approval with the Food and Drug Administration by 2001, according to a statement released by Eli Lilly and Co.
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From Sepracor website:(R)-fluoxetine has potential advantages over existing therapies for treatment of psychiatric disorders. The drug has potential for improved efficacy and new indications such as depression, OCD, anxiety spectrum disorders, eating disorders such as obesity and anorexia as well as PMS. (R)-fluoxetine has the potential for increased tolerability in treating anxiety and sexual dysfuntion. In addition, it is a preferred platform for combination therapies due to its faster onset and improved efficacy. In December 1998, Sepracor and Eli Lilly and Company announced a licensing agreement, that will enable Lilly to exclusively develop and globally commercialize R-fluoxetine. R-fluoxetine, a new chemical entity patented by Sepracor, is a modified form of an active ingredient found in Prozac.
poster:SLS
thread:43425
URL: http://www.dr-bob.org/babble/20000811/msgs/43457.html