Klaus Schmiegel

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Klaus Schmiegel
Born (1939-06-28) June 28, 1939 (age 84)
Chemnitz, Germany
NationalityGerman
Alma mater University of Michigan (B.S.)
Dartmouth College (A.M.)
Stanford University (Ph.D)
Known forInventing fluoxetine, the active ingredient in Prozac
Awards National Inventors Hall of Fame, 1999
American Innovator Award, 1999
Scientific career
Fields Chemistry

Klaus Schmiegel (born June 28, 1939), is a German chemist best known for his work in organic chemistry, which led to the invention of Prozac, a widely used antidepressant.

Contents

Biography

Early life and education

Klaus Schmiegel was born in Chemnitz, Germany on June 28, 1939. After he immigrated to the United States in 1951, Schmiegel received a B.S. in chemistry from the University of Michigan, an A.M. in organic chemistry from Dartmouth College, and a Ph.D. in organic chemistry from Stanford University. [1] His strong educational background secured him a prestigious position as a senior organic chemist at Eli Lilly, a prominent pharmaceutical company.

Primary accomplishment

At Eli Lilly in the 1960s, Schmiegel and Bryan Molloy, with the help of David Wong, searched for a compound to combat depression. Because depression and similar psychiatric disorders are associated with reduced serotonin levels[ citation needed ], they focused their approach on prohibiting serotonin reuptake. During a regular nerve signal transmission, a neurotransmitter such as serotonin travels from a presynaptic neuron to a postsynaptic neuron; the neurotransmitter returns to the presynaptic neuron after fulfilling its function, the reuptake process. Therefore, slowing and diminishing serotonin reuptake boosts serotonin levels in the brain.

The scientists based their search on the template of the antihistamine drug diphenhydramine hydrochloride, commonly known as Benadryl. After many failures, the research team synthesized a group of compounds called aryloxyphenylpropylamines. Upon testing, a member of the group, fluoxetine hydrochloride, proved to affect only the neurotransmitter serotonin. This compound became the first selective serotonin reuptake inhibitor (SSRI) and the active ingredient in the vastly popular and effective drug Prozac. [2]

Prozac, the "Drug Of Despair"

Eli Lilly recognized the potential of its new drug, but the company first tested it as a high blood pressure medication, an anti-obesity drug, and a remedy for severe depression. After those testing failures, Eli Lilly succeeded in treating five mildly depressed people; fluoxetine had found its niche. Eli Lilly announced its findings in 1974 and launched Prozac in 1987 after receiving FDA approval.

The “wonder drug” replaced earlier medications, tricyclic antidepressants, which were less effective with serious side effects such as headaches, blurred vision and hypertension. By 1999, Prozac was bringing in $2.5 billion per year, 25% of Eli Lilly's revenue. The drug helped erase the stigma of depression, inspiring celebrities and public figures to flaunt rather than hide their sufferings.

Prozac, which is recognized by Fortune magazine as a “Product of the Century,” has few side effects; it has been widely beneficial for those suffering from depression, obsessive compulsive disorders, panic disorders, eating disorders and premenstrual dysphoric disorders. However, some contend that Prozac has been doled out too liberally—it has even been prescribed for animals. Peer drugs, including Zoloft and Paxil, which are also SSRIs, have experienced similar successes.

Unfortunately for Eli Lilly, its patent on Prozac expired in 2001, causing massive revenue losses. The company hopes to bounce back with its newest drug, Cymbalta, a painkiller and an antidepressant combined. [3]

Other scientific work

Schmiegel is listed as an inventor on all eighteen of his patents, and his patents are assigned to his company, Eli Lilly. Schmiegel's chemical work concentrated on supplements to bolster the health of animals (growth promotion), weight control agents, and antidepressants. [4]

Awards and recognition

In 1999, both Schmiegel and Molloy were inducted into the National Inventors Hall of Fame for their fluoxetine compound that revolutionized depression treatment. [5] In addition, the same year, the pair received the U.S. Department of Commerce's Ronald H. Brown American Innovator award, honoring their great contribution to society. [6]

Later years

Schmiegel worked for Eli Lilly until his retirement in 1993. Though Schmiegel is retired, he still lives in Indianapolis near the Eli Lilly headquarters.

Related Research Articles

<span class="mw-page-title-main">Antidepressant</span> Class of medication used to treat depression and other conditions

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<span class="mw-page-title-main">Psychopharmacology</span> Study of the effects of psychoactive drugs

Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.

<span class="mw-page-title-main">Monoamine transporter</span> Proteins that function as integral plasma-membrane transporters

Monoamine transporters (MATs) are proteins that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. The three major classes are serotonin transporters (SERTs), dopamine transporters (DATs), and norepinephrine transporters (NETs) and are responsible for the reuptake of their associated amine neurotransmitters. MATs are located just outside the synaptic cleft (peri-synaptically), transporting monoamine transmitter overflow from the synaptic cleft back to the cytoplasm of the pre-synaptic neuron. MAT regulation generally occurs through protein phosphorylation and post-translational modification. Due to their significance in neuronal signaling, MATs are commonly associated with drugs used to treat mental disorders as well as recreational drugs. Compounds targeting MATs range from medications such as the wide variety of tricyclic antidepressants, selective serotonin reuptake inhibitors such as fluoxetine (Prozac) to stimulant medications such as methylphenidate (Ritalin) and amphetamine in its many forms and derivatives methamphetamine (Desoxyn) and lisdexamfetamine (Vyvanse). Furthermore, drugs such as MDMA and natural alkaloids such as cocaine exert their effects in part by their interaction with MATs, by blocking the transporters from mopping up dopamine, serotonin, and other neurotransmitters from the synapse.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), and migraine prevention. SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

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<span class="mw-page-title-main">Olanzapine/fluoxetine</span> Antidepressant medication

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<span class="mw-page-title-main">Fluoxetine</span> SSRI antidepressant

Fluoxetine, sold under the brand name Prozac, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorder (OCD), anxiety, bulimia nervosa, panic disorder, and premenstrual dysphoric disorder. It is also approved for treatment of major depressive disorder in adolescents and children 8 years of age and over. It has also been used to treat premature ejaculation. Fluoxetine is taken by mouth.

A serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), is a type of drug that acts as a combined reuptake inhibitor of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine. It does this by concomitantly inhibiting the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT), respectively. Inhibition of the reuptake of these neurotransmitters increases their extracellular concentrations and, therefore, results in an increase in serotonergic, adrenergic, and dopaminergic neurotransmission. The naturally-occurring and potent SNDRI cocaine is widely used recreationally and often illegally for the euphoric effects it produces.

<span class="mw-page-title-main">Serotonin reuptake inhibitor</span> Class of drug

A serotonin reuptake inhibitor (SRI) is a type of drug which acts as a reuptake inhibitor of the neurotransmitter serotonin by blocking the action of the serotonin transporter (SERT). This in turn leads to increased extracellular concentrations of serotonin and, therefore, an increase in serotonergic neurotransmission. It is a type of monoamine reuptake inhibitor (MRI); other types of MRIs include dopamine reuptake inhibitors and norepinephrine reuptake inhibitors.

<span class="mw-page-title-main">Seproxetine</span> SSRI drug and metabolite of fluoxetine

Seproxetine, also known as (S)-norfluoxetine, is a selective serotonin reuptake inhibitor (SSRI). It is the S enantiomer of norfluoxetine, the main active metabolite of the widely used antidepressant fluoxetine; it is nearly 4 times more selective for stimulating neurosteroid synthesis relative to serotonin reuptake inhibition than fluoxetine. It is formed through the demethylation, or removal of a methyl group, of norfluoxetine. Seproxetine is both an inhibitor of serotonin and dopamine transporters, 5-HT2A and 5-HT2C receptors. It was being investigated by Eli Lilly and Company as an antidepressant; however, it inhibited the KvLQT1 protein, which is responsible for the management of the QT interval. This is the time it takes for the heart to contract and recover. Due to the inhibition, the QT interval was prolonged, which could lead to significant cardiac side complications. Due to this, development of the medication was discontinued. Tests on its efficacy found that it was equivalent to fluoxetine, but sixteen times more powerful than the R enantiomer of norfluoxetine.

<span class="mw-page-title-main">Nisoxetine</span> Chemical compound

Nisoxetine, originally synthesized in the Lilly research laboratories during the early 1970s, is a potent and selective inhibitor for the reuptake of norepinephrine (noradrenaline) into synapses. It currently has no clinical applications in humans, although it was originally researched as an antidepressant. Nisoxetine is now widely used in scientific research as a standard selective norepinephrine reuptake inhibitor. It has been used to research obesity and energy balance, and exerts some local analgesia effects.

<span class="mw-page-title-main">Selective serotonin reuptake inhibitor</span> Class of antidepressant medication

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.

Selective serotonin reuptake inhibitors, or serotonin-specific re-uptake inhibitor (SSRIs), are a class of chemical compounds that have application as antidepressants and in the treatment of depression and other psychiatric disorders. SSRIs are therapeutically useful in the treatment of panic disorder (PD), posttraumatic stress disorder (PTSD), social anxiety disorder, obsessive-compulsive disorder (OCD), premenstrual dysphoric disorder (PMDD), and anorexia. There is also clinical evidence of the value of SSRIs in the treatment of the symptoms of schizophrenia and their ability to prevent cardiovascular diseases.

<span class="mw-page-title-main">PPPA (drug)</span> Chemical compound

PPPA, or 3-phenoxy-3-phenylpropan-1-amine, is a drug which is described as an antidepressant. It was derived by Eli Lilly from the antihistamine diphenhydramine, a diphenylmethane derivative with additional properties as a selective serotonin reuptake inhibitor (SSRI), and has been the basis for the subsequent discovery of a number of other antidepressant drugs.

<i>N</i>-Methyl-PPPA Chemical compound

N-Methyl-PPPA, or N-methyl-3-phenoxy-3-phenylpropan-1-amine, is a serotonin-norepinephrine reuptake inhibitor (SNRI) which was developed by Eli Lilly from diphenhydramine in the early 1970s while in search of new antidepressants, but was never marketed. It is closely related structurally to fluoxetine, atomoxetine, and nisoxetine.

Bryan Barnet Molloy was a Scottish chemist, known notably for helping to invent the antidepressant Prozac, a name for fluoxetine. Prozac was introduced in 1988, and has been the world's leading antidepressant.

Selective norepinephrine reuptake inhibitors (sNRIs) are a class of drugs that have been marketed as antidepressants and are used for various mental disorders, mainly depression and attention-deficit hyperactivity disorder (ADHD). The norepinephrine transporter (NET) serves as the fundamental mechanism for the inactivation of noradrenergic signaling because of the NET termination in the reuptake of norepinephrine (NE). The selectivity and mechanism of action for the NRI drugs remain mostly unresolved and, to date, only a limited number of NRI-selective inhibitors are available. The first commercially available selective NRI was the drug reboxetine (Edronax), developed as a first-line therapy for major depressive disorder. Atomoxetine (Strattera) is another potent and selective NRI which is also effective and well tolerated for the treatment of ADHD in adults; it may also be a new treatment option for adults with ADHD, particularly for those patients at risk of substance abuse.

References

  1. "Klaus Schmiegel | Lemelson". lemelson.mit.edu. Retrieved 2023-07-06.
  2. "Chemical & Engineering News: Top Pharmaceuticals: Prozac". pubsapp.acs.org. Retrieved 2023-07-06.
  3. Moore, Anna (2007-05-13). "Eternal sunshine". The Observer. ISSN   0029-7712 . Retrieved 2023-07-06.
  4. "Klaus K. Schmiegel Inventions, Patents and Patent Applications - Justia Patents Search". patents.justia.com. Retrieved 2023-07-06.
  5. "NIHF Inductee Klaus Schmiegel Invented Prozac Medication". www.invent.org. 2023-07-06. Retrieved 2023-07-06.
  6. "United States Patent and Trademark Office 1999 Annual Report" (PDF). Retrieved July 6, 2023.