Lily Is Looking at Possible "Prozac" of Antipsychotic Drugs

Drug companies such as Lilly are always looking for the "big score," like Lilly had with Prozac. Prozac was first in its class of the low side effect SSRI antidepressants, that largely replaced the more dangerous tricyclics and MAO inhibitors.

If results of a recent trial hold up, a new Lilly drug LY2140023 may be the prototype, first in its class, new anti-psychotic--without the troubling side effects of current anti-psychotics.

...According to the authors, the trial "provides strong new evidence for the role of glutamate modulation in treating psychosis, and specifically for mGlu2/3 receptor activation as a viable therapeutic approach to treat schizophrenia."

Crucially, LY2140023 has a very different adverse effect (AE) profile than the company's blockbuster antipsychotic Zyprexa (olanzapine), which had 2005 sales of over $4bn (€2.9bn).

Eli Lilly has been hit by a series of lawsuits over the side effects of olanzapine and has agreed to pay at least $1.2bn to 25,000 claimants.


...Most antipsychotic and atypical antipsychotic drugs, including olanzapine, work by affecting the dopamine and serotonin neurotransmitter pathways.

In contrast, LY2140023 works as a receptor agonist for the glutamate system, specifically targeting the metabotropic glutamate 2/3 (mGlu2/3) receptor to reduce the presynaptic release of the glutamate neurotransmitter in brain regions where mGlu2/3 receptors are expressed.

LY2140023 is a methionine amide oral pro-drug which is readily hydrolysed to form Eli Lilly's earlier candidate LY404039 which suffered from poor human oral absorption.

The trial, that included 196 patients suffering from schizophrenia, compared the effects of the new drug to placebo, as well as including olanzipine as an active control.

Treatment with LY2140023 was not observed to cause certain common AEs associated with schizophrenia treatments such as increased prolactin elevations, extrapyramidal symptoms and weight that occur with currently approved schizophrenia medications.

Drug Researcher

The target population for this drug would be schizophrenics and other psychotics. It is likely that other psychiatric and neurologic conditions will be amenable to mGlu2/3 receptor agonists, if the side effect profile is truly as advertised.

Only someone who has watched a schizophrenic recover much of his mental function on anti-psychotics, only to suffer from debilitating--even fatal--side effects from treatment, would appreciate the promise of a truly efficacious anti-psychotic with a benign side effect profile. If Lilly truly has come up with the "Prozac" of anti-psychotics, I wish them good fortune for it.