Phil Skolnick (born 26 February 1947) is an American

neuroscientist A neuroscientist (or neurobiologist) is a scientist who has specialised knowledge in neuroscience, a branch of biology that deals with the physiology, biochemistry, psychology, anatomy and molecular biology of neurons, Biological neural network, n ...

and

pharmacologist Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

most widely known for his work on the

psychopharmacology Psychopharmacology (from Greek grc, ψῡχή, psȳkhē, breath, life, soul, label=none; grc, φάρμακον, pharmakon, drug, label=none; and grc, -λογία, -logia, label=none) is the scientific study of the effects drugs have on m ...

of depression and

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

, as well as on

addiction medicine Addiction medicine is a medical subspecialty that deals with the diagnosis, prevention, evaluation, treatment, and recovery of persons with addiction, of those with substance-related and addictive disorders, and of people who show unhealthy us ...

. Author of more than 500 published papers, Skolnick's most notable accomplishments include elucidating the role of the

NMDA ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...

system in depression therapeutics, demonstrating the existence of endogenous benzodiazepine receptor ligands, and spearheading the

National Institute on Drug Abuse The National Institute on Drug Abuse (NIDA) is a United States federal government research institute whose mission is to "advance science on the causes and consequences of drug use and addiction and to apply that knowledge to improve individual a ...

's partnership to develop a

naloxone Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse or reduce the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin within ...

atomizer for reversal of acute

opioid overdose An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to respiratory depression, a lethal condition that ca ...

. Skolnick's work also laid the foundation for the development of

ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...

as a

rapid-acting antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, heada ...

Early life and education

Raised in a Manhattan

tenement A tenement is a type of building shared by multiple dwellings, typically with flats or apartments on each floor and with shared entrance stairway access. They are common on the British Isles, particularly in Scotland. In the medieval Old Town, i ...

, Skolnick attended

Stuyvesant High School Stuyvesant High School (pronounced ), commonly referred to among its students as Stuy (pronounced ), is a State school, public university-preparatory school, college-preparatory, Specialized high schools in New York City, specialized high school ...

, one of New York City's most selective specialized high schools. Graduating at the age of 16, he began attending

Long Island University Long Island University (LIU) is a private university with two main campuses, LIU Post and LIU Brooklyn, in the U.S. state of New York. It offers more than 500 academic programs at its main campuses, online, and at multiple non-residential. LIU ...

in 1964. After graduating

summa cum laude Latin honors are a system of Latin phrases used in some colleges and universities to indicate the level of distinction with which an academic degree has been earned. The system is primarily used in the United States. It is also used in some Sou ...

in 1968, he attended George Washington University's school of medicine in

Washington, D.C. ) , image_skyline = , image_caption = Clockwise from top left: the Washington Monument and Lincoln Memorial on the National Mall, United States Capitol, Logan Circle, Jefferson Memorial, White House, Adams Morgan, ...

receiving a PhD in pharmacology.

Career

National Institutes of Health

Shortly after graduating from GWU in 1972, Skolnick was brought on as a staff

fellow A fellow is a concept whose exact meaning depends on context. In learned or professional societies, it refers to a privileged member who is specially elected in recognition of their work and achievements. Within the context of higher education ...

at what is now the

National Institute of Diabetes and Digestive and Kidney diseases The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is part of the United States National Institutes of Health, which in turn is part of the Department of Health and Human Services. NIDDK is approximately the fifth-largest ...

(NIDDK), a subdivision of the

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

(NIH), where he was mentored by John Daly. In 1983, Skolnick became section chief of NIDDK's neurobiology laboratory, rising to the role of Chief of the NIDDK Laboratory of Neuroscience in 1986. During his time at NIH, Skolnick trained more than 75 postdocs.

Anxiety: barbiturate and benzodiazepine systems

In 1981, Skolnick and colleague Steven M. Paul characterized the mechanism of action of benzodiazepines, showing that they act by modifying the efficacy of the brain's primary inhibitory neurotransmitter, GABA. The following year, Skolnick and Paul, among other collaborators, showed that mammalian brain tissue contains endogenous ligands of the benzodiazepine receptor, some of the first evidence of so-called endozepines. In 1985, not long after becoming section chief of NIDDK's neurobiology lab, Skolnick and colleagues published work helping to characterize the mechanism of action of barbiturates, which function as positive allosteric modulators at the GABA_A receptor—a mechanism of action they share with benzodiazepines. Later, inspired by similarities between the

electroencephalographic Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...

signatures associated with

hepatic coma Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages ...

and benzodiazepine-induced coma, Skolnick hypothesized that impaired metabolism of endogenous benzodiazepine receptor ligands may play a role in producing the symptoms of hepatic encephalopathy. This hypothesis was borne out by experimental research, where it was shown that benzodiazepine receptor

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

s can temporarily alleviate some of the cognitive symptoms of fulminant hepatic failure.

NMDA systems, depression, aminoglycosides

By the late 1980s, it was known that certain types of stress induce a behavioral profile in animals that bears a strong resemblance to the symptoms of clinical depression, and that symptoms in this experimental model respond to antidepressants such as

SSRIs 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. SSRIs increase the extracellul ...

. This depression-like effect arises, in part, through prolonged stimulation of the

subtype of the

glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system a ...

. This led Skolnick and colleagues to discover in 1990 that inhibition of activity at the NMDA receptor (NMDAr) can prevent the development of this depression-like behavior, suggesting NMDA receptor antagonists—such as ketamine—as novel antidepressant therapies. In 1996, Skolnick and one of his postdoctoral students, Anthony Basile, developed the hypothesis that off-site activity of

aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...

antibiotics, which also have the potential to land on the NMDA receptor, might be responsible for the drugs' undesirable

ototoxic Ototoxicity is the property of being toxic to the ear (''oto-''), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and temporary, ...

side-effects. Skolnick and Basile proved this hypothesis by counteracting the ototoxic effects of aminoglycosides using an NMDAr antagonist.

Eli Lilly & Company

In 1997, 25 years after joining the NIH, Skolnick was recruited by former collaborator Steven M. Paul to become a Lilly Fellow in Neuroscience at

Eli Lilly & Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...

, where he worked toward the development of novel therapeutics for depression, applying the principles of

rational drug design Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activa ...

to synthesize and investigate new molecules.

DOV Pharmaceuticals

In 2001, Skolnick left Lilly for the New Jersey-based

DOV Pharmaceutical DOV Pharmaceutical was a biotechnology company that focused on therapies primarily for central nervous system conditions. It was founded in 1995 by former employees of American Cyanamid (which was acquired by Wyeth in 1994), and in 1998 it in-lic ...

, where he acted as Chief Scientific Officer and Senior Vice President of Research. During his tenure at DOV, Skolnick oversaw development and testing of a variety of novel drugs, including the anti-anxiety candidate molecule DOV 51892—an "anxioselective" compound which is designed to produce the anxiety-alleviating effects of typical anxiolytics, but without the sedative side-effects usually characteristic of this class of drug. In addition to his role as the CSO and Senior Vice President of Research, Skolnick became president of DOV Pharmaceutical in 2007 before departing in 2009.

National Institute on Drug Abuse

After his tenure at DOV, Skolnick returned to the NIH in 2010, this time as the director of the

's Division of Therapeutics and Medical Consequences (DTMC), which focuses largely on pharmacological therapies for addiction. Most notably, Skolnick's time at NIDA saw the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

approval and deployment of the Narcan nasal spray tool, an easy-to-use

reversal device developed in partnership with Lightlake Therapeutics. Narcan nasal spray is intended for distribution to the general public, allowing the friends or family of an overdose victim to counteract the drug's effects almost immediately, without waiting for emergency response personnel to arrive. Many lives are lost due to drug users' hesitance to contact emergency services, a trend which Narcan nasal spray may help combat.

Opiant Pharmaceuticals

In early 2017, Skolnick re-retired from NIH to serve as Chief Scientific Officer of Opiant Pharmaceuticals, Inc.—manufacturers of the Narcan nasal spray device.

References

External links

IBNS Bench-to-Bedside Thursday Lecture: Phil Skolnick
June 28, 2013 {{DEFAULTSORT:Skolnick, Phil 1947 births Living people American neuroscientists Long Island University alumni George Washington University School of Medicine & Health Sciences alumni