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Re: SSRI chronology

Posted by djmmm on January 12, 2007, at 6:48:10

In reply to Re: SSRI chronology, posted by SLS on January 12, 2007, at 6:13:58

> > I always thought Prozac was the first SSRI. Apparently Luvox was released in Switzerland already in 1984.
> >
> > Klavot
> Zimelidine was released before fluvoxamine (Luvox), but was withdrawn due to the appearance of the sometimes fatal Guillain-Barré syndrome.
> Indalpine may have been released first in France before fluvoxamine and zimelidine, but I'm not sure.
> - Scott

This is interesting, and very helpful...

"History of Modern Psychopharmacology: A Personal View With an Emphasis on Antidepressants"

Edward F. Domino, MD

an excerpt..

"Selective Serotonin Reuptake Inhibitors as Antidepressants"

"Although most pharmacologists by the 1960s thought the primary mode of action of tricyclic antidepressants was to inhibit norepinephrine reuptake, some reexamined the actions of diverse antihistamines on the reuptake of various biogenic amines, especially serotonin. The serotonin hypothesis of depression was championed only by very few psychiatrists, such as Coppen in England (50). Isaac and Goth (51, 52) found that tripelennamine (Pyribenamine®), d-chlorpheniramine (Polaramine®), and diphenhydramine all had cocaine-like effects in reducing [3H]-norepinephrine uptake which did not correlate with their antihistaminic actions. Subsequently, Barnett et al. (53) studied 19 different antihistamines in a series of animal tests for antidepressant action. About half of the compounds showed potential antidepressant effects. Again, there was no correlation with their antidepressant and antihistamine activities. In 1969, Carlsson and Lindqvist (54) studied selected opioid analgesics and antihistamines as monoaminergic reuptake blockers with emphasis on interactions with serotonin, its precursor 5-hydroxytryptophan, and the MAO inhibitor, nialamide. Several antihistaminics showed considerable activity, especially chlorpheniramine, but more on norepinephrine than serotonin reuptake. They noted that diphenhydramine was inactive against norepinephrine but active against serotonin. In 1969, two Russian pharmacologists, Lapin and Oxenkrug, the latter now in the U.S., proposed an increase in brain serotonergic mechanisms as a determinant of antidepressant effects (55). They summarized evidence that an increase in brain noradrenergic mechanisms caused the energizing and motor stimulating effects of the then available antidepressants, but an increase in serotonergic mechanisms was responsible for their mood-elevating effects. A year later, Molloy and Rathburn at Eli Lilly began a search for structural analogs of diphenhydramine as possible antidepressants. Their research approach was very rational inasmuch as it was based on the above reports that certain antihistamines, including diphenhydramine, were inhibitors of serotonin reuptake and had antidepressant properties in laboratory models. The phenoxyphenylpropylamine structure was Eli Lilly’s basic molecule for chemical substitutions. It is drawn so as to compare it with the substituted methoxyethylamine antihistamines such as diphenhydramine. Wong et al. (56, 57) summarized the development of fluoxetine, the first SSRI, as an antidepressant drug. With the phenomenal clinical and commercial success of fluoxetine as an antidepressant, many other pharmaceutical companies quickly developed their own exclusive SSRI."




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