Seeman, Philip

/

Professor Emeritus

BSc, MSc, MDCH, PhD Philip Seeman, MD, Ph.D. OC, FRSC (February 8 1934 - January 9 2021). Professor, Dept. of Pharmacology, U of T. Neuropharmacologist and schizophrenia researcher well known for his research on dopamine receptors.

Published obituaries:

1 PHILIP SEEMAN 1934 - 2021 Philip Seeman died at home on January 9 after a very long progressive muscle disease. His disability did not stop him from continuing to publish, until late 2020, on his favourite topics, the dopamine hypothesis of schizophrenia and the molecular mechanisms of action of old and new antipsychotic drugs. Philip was never happy unless he was helping someone, whether a family member, a student, a colleague, or, as happened often, a stranger who asked for advice and counsel. Philip is beloved by his wife, Mary, his children, Marc (Ellen), Bob (Nicola), and Neil (Sarit) his six grandchildren, Ahron, Geoffrey, Ciara, David, Ronan, and Dori, his niece Carolyn, nephews Martin and Cooper, several cousins, and large numbers of grandnieces and nephews. As a result of Philip's pioneering work in discovering the configuration of the dopamine receptor in the brain to which antipsychotic drugs attach, schizophrenia and related diseases have been greatly destigmatized. The many who daily battle with these diseases are now able to live with dignity and respect. Funeral services will be private. To honour Philip's memory, donations may be directed to schizophrenia research at the Centre for Addiction and Mental Health. Published in The Globe and Mail from Jan. 16 to Jan. 20, 2021. https://www.legacy.com/obituaries/theglobeandmail/obituary.aspx?pid=197516322

2: In memoriam professor Philip Seeman (February 8, 1934-January 9, 2021)

Professor Philip Seeman MD, PhD, DSc FRSC, Order of Canada, an ACNP Member Emeritus, was a towering icon of neuropsychiatric research. Inspired by his beloved wife and psychiatrist Dr. Mary V. Seeman, Philip became intrigued with schizophrenia pathophysiology. With the advent of effective antipsychotic drugs (e.g., haloperidol), he surmised that their targets could guide the path towards illuminating the pathology of schizophrenia. He acquired a radiolabeled form of haloperidol from its inventor, Dr. Paul Janssen. In 1974 he reported a seminal discovery that captivated the field of schizophrenia research: antipsychotic medications bound haloperidol-labeled sites at concentrations and with a rank order of potencies that correlated with the mean daily antipsychotic doses taken by patients with schizophrenia. He named the sites antipsychotic/dopamine receptors (later designated dopamine D2 receptors), based on the potency of dopamine. This achievement provided direct evidence for dopamine receptors, their relevance to antipsychotic drug activity and schizophrenia. It transformed dopamine receptor research by enabling in vitro screening for new antipsychotic drugs, by catalyzing the discovery of five dopamine receptor subtypes by cloning, and investigation of receptor subtype relevance to schizophrenia, Parkinson’s disease, Huntington’s Disease, addictive processes and endocrine disorders. Imaging of the D2 dopamine receptor in living human brain became feasible, and enabled discovery of the minimum D2 receptor occupancy (65%) for antipsychotic benefit, of the relevance of the D2 dopamine receptor to neuropsychiatric diseases, to addictive processes, to drug response, drug discovery, and measures of dopamine release. Dr. Seeman showed that many atypical antipsychotics rapidly dissociated from the D2 dopamine receptor, which he postulated could account for their diminished adverse neurological side effects; rapid offset times conceivably enabled periodic dopamine receptor activity and cycling to reduce maladaptations arising from uninterrupted receptor blockade. In later years, he found evidence for supersensitive D2 receptors in animal models of psychosis, which he postulated could explain the therapeutic benefit of D2 receptor blockade. In GWAS schizophrenia research, the D2 dopamine receptor gene has been ranked as highly associated with the disease. Current evidence indicates that polygenic mutations, brain injury, drug use, prenatal infection and malnutrition, social isolation and marginalization, are associated with symptoms of schizophrenia. Nonetheless, dopamine circuits are likely to constitute a final common route to many of the clinical symptoms, as they generally are alleviated by drugs that block dopamine D2 receptors.

Dr. Seeman cherished scientific research and practiced it compulsively and pragmatically. His 1980 review of dopamine receptors contained 1278 references, which he alone acquired in hard copy, cataloged by topic, read and underlined key sentences long before electronic media enabled keypress access to articles. He focused on core mechanisms and pathological unknowns, diagnostics and therapeutics. The impact of his research was recognized internationally. He was made an Officer of the Order of Canada and received numerous awards in Canada, the United States and in other nations. Dr. Seeman’s towering research accomplishments live on in servers hosting ~800 articles and 56,000 citations (Google Scholar), and in a legacy of mentoring over 100 students, post-doctoral fellows and trainees. Philip Seeman’s intangible traits - generosity, kindness, mentorship, friendship, equanimity, and humor - live on in the memories of those fortunate enough to have known him as a friend, a trainee, a colleague, an advisor, a collaborator.

nature neuropsychopharmacology in memoriam article McLean Hospital, Department of Psychiatry, Harvard Medical School, Belmont, MA, 02478, USA Bertha Madras

University of Toronto, Molecular Pharmacology, Toronto, ON, M5S 1A8, Canada Susan George

Corresponding author Correspondence to Bertha Madras.

Additional information Our heartfelt sympathy extend to his wife, professor Mary V. Seeman and other family members.

About this article Madras, B., George, S. In memoriam professor Philip Seeman (February 8, 1934-January 9, 2021). Neuropsychopharmacol. 46, 1229–1230 (2021). https://doi.org/10.1038/s41386-021-00975-x https://www.nature.com/articles/s41386-021-00975-x

Other Postings:

1: Philip Seeman, M.D., Ph.D. Professor of Pharmacology and Psychiatry University of Toronto

In 1975, Dr. Seeman discovered the antipsychotic dopamine receptor, now called the dopamine D2 receptor. Later, he showed that atypical antipsychotics such as Clozaril® or Seroquel® dissociated from the D2 receptor more quickly than traditional antipsychotics such as Haldol® or Thorazine®. He discovered that the dopamine super-sensitivity is based on a marked increase in the proportion of antipsychotic D2 receptors in a state of high-affinity for dopamine (D2High receptors). This elevation occurs in all known animal models of psychosis. Antipsychotic drugs such as Haldol® can inhibit the rise in amphetamine-induced elevation of these D2High receptors. He recently showed that the new type of glutamate drug (LY404039) being tested for treating schizophrenia also has a significant affinity for the dopamine D2High receptor.

Since 1967, Dr. Seeman has been at the University of Toronto, Department of Pharmacology and served as its Chair between 1977 and 1987. BBRF Awards & Recognition Scientific Council Member Emeritus (Joined 1994) 2000, 1995, 1988 Distinguished Investigator Grant 1990 Lieber Prize for Outstanding Achievement in Schizophrenia Research Reprinted from: https://www.bbrfoundation.org/about/people/philip-seeman-md-phd

2: Philip Seeman Emeritus Professor University of Toronto, Department of Pharmacology and Toxicology Toronto, ON, M5P 3L6 APPOINTMENT STATUS PRIMARY

Philip Seeman received an M.D. from McGill and a Ph.D. from Rockefeller University. Since 1967 he has been in the University of Toronto Departments of Pharmacology and Psychiatry. He has held the Pharmacology Chair, and a University Tanenbaum Chair in Neuroscience.

He has trained over 120 graduate students and Fellows. He has received 25 awards, including the Lieber Award of NARSAD, the Lifetime Achievement Award of the Society for Biological Psychiatry, the Stanley Dean Award of the American College of Psychiatrists, the Prix Galien award, the Pasarow award in Neuropsychiatry, the Killam Prize, and the Order of Canada.

Reproduced from: https://www.psychiatry.utoronto.ca/faculty/philip-seeman

3: From Wikipedia, the free encyclopedia

Philip Seeman Born 8 February 1934 Winnipeg, Manitoba, Canada Died 9 January 2021 (aged 86) Toronto, Ontario, Canada Awards Order of Canada Philip Seeman, OC FRSC (8 February 1934 – 9 January 2021) was a Canadian schizophrenia researcher and neuropharmacologist, known for his research on dopamine receptors.[1]

Contents 1 Career 2 Notes 3 References 4 External links

Career Born in Winnipeg, Manitoba, Seeman was raised in Montreal. He received a Bachelor of Science degree, honours physics & physiology (1955), a Master of Science degree, physiology of transport & secretion (1956), and a Doctor of Medicine (1960) from McGill University. In 1966, he received a Ph.D. in life sciences from Rockefeller University.

In 1967, Seeman became an assistant professor in the Department of Pharmacology at the University of Toronto. In 1970, he was appointed a professor.

In 1974, having spent years in search of the binding site of antipsychotic medication, he discovered the dopamine D2 receptor, the basis for the dopamine hypothesis of schizophrenia.[2][3]

In 2001, he was made an Officer of the Order of Canada "for his research on dopamine receptors and their involvement in diseases such as schizophrenia, Parkinson's and Huntington's".[4]

In 1985, he was made a Fellow of the Royal Society of Canada.[5]

He was married to Dr. Mary V. Seeman.[6]

Notes

"Philip SEEMAN". The Globe and Mail. Retrieved 19 January 2021.
P. Seeman, M. Chau-Wong, J. Tedesco & K. Wong (November 1975). "Brain receptors for antipsychotic drugs and dopamine: direct binding assays". Proceedings of the National Academy of Sciences of the United States of America. 72 (11): 4376–4370. Bibcode:1975PNAS...72.4376S. doi:10.1073/pnas.72.11.4376. PMC 388724. PMID 1060115.
"People". CMAJ. 151 (8): 1186–1187. 1994. PMC 1337253.
Order of Canada citation
http://www.sciandmed.com/sm/journalviewer.aspx?issue=1066&article=787&action=1
"Most Wikipedia profiles are about men – these women in Australia are hoping to change that". SBS News. Retrieved 27 July 2019.

References Madras, B.K. (2013). "History of the discovery of the antipsychotic dopamine D2 receptor: A basis for the dopamine hypothesis of schizophrenia". Journal of the History of the Neurosciences: Basic and Clinical Perspectives. 22 (1): 62–78. doi:10.1080/0964704x.2012.678199. PMID 23323533. Seeman, P. (2011). "All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2High receptors". CNS Neuroscience and Therapeutics. 17 (2): 118–132. doi:10.1111/j.1755-5949.2010.00162.x. PMC 6493870. PMID 20560996. P. Seeman (2010). "Dopamine D2 Receptors as Treatment Targets in Schizophrenia. Clinical Schizophrenia & Related Psychoses April: 56-73. P. Seeman (2007), Scholarpedia, 2(10): 3634 doi.4249/scholarpedia.3634 Seeman, P. (2006). "Targeting the dopamine D2 receptor in schizophrenia". Expert Opinion on Therapeutic Targets. 10 (4): 515–531. doi:10.1517/14728222.10.4.515. PMID 16848689. Seeman, P.; Weinshenker, D.; Quirion, R.; Srivastava, L.; Bhardwaj, S.K.; Grandy, D.K.; Premont, R.; Sotnikova, T.; Boksa, P.; El-Ghundi, M.; O'Dowd, B.F.; George, S.R.; Perreault, M.L.; Mannisto, P.T.; Robinson, S.; Palmiter, R.D.; Tallerico, T. (2005). "Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis". Proceedings of the National Academy of Sciences USA. 102 (9): 3513–3518. Bibcode:2005PNAS..102.3513S. doi:10.1073/pnas.0409766102. PMC 548961. PMID 15716360. Seeman, P.; Chau-Wong, M.; Tedesco, J.; Wong, K. (1975). "Brain receptors for antipsychotic drugs and dopamine: Direct binding assays". Proceedings of the National Academy of Sciences, USA. 72 (11): 4376–4380. Bibcode:1975PNAS...72.4376S. doi:10.1073/pnas.72.11.4376. PMC 388724. PMID 1060115. External links Home Page of Philip Seeman's Laboratory Probing the Biology of Psychosis, Schizophrenia, and Antipsychotics: An Expert Interview With Dr. Philip Seeman, MD, PhD – an interview on the Medscape website Schizophrenia – an essay by Philip Seeman, November 2001 Authority control Edit this at Wikidata NKC: mub2015888069VIAF: 492144783073059045433WorldCat Identities: viaf-492144783073059045433 Categories: 1934 births2021 deathsCanadian pharmacologistsFellows of the Royal Society of CanadaOfficers of the Order of CanadaPeople from WinnipegSchizophrenia researchersNeuropharmacologistsCanadian neuroscientists This page was last edited on 7 February 2021, at 01:11 (UTC). Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.

Reprinted from: https://en.wikipedia.org/wiki/Philip_Seeman