Benjamin Weiss Ph.D., Father of Phosphodiesterase Drug Inhibition

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Benjamin Weiss
Born January 26,  1937

The Bronx, New York City, NY, USA

Nationality United States
Alma mater Philadelphia College of Pharmacy and Science (Now called University of the Sciences, Philadelphia, Pennsylvania)
Known for Neuropharmacology; Phosphodiesterase inhibition
Awards 1958        Gold Medal for Attaining Highest Scholastic Average of College Graduates

1958        Joseph W. E. Harrison Award for Excellence in Pharmacology

1958        Frederick William Haussman Memorial Prize

1958        Dobbins Scholarship

1959        Rexall Award

1959        Borden Award

1959        Rho Chi Honorary Pharmaceutical Society

1980        Christian R. and Mary F. Lindback Award for Distinguished Teaching

1981         Named by the Institute for Scientific Information as one of the Top One Thousand                 Most Quoted Contemporary Scientists in the World

1982        Research Medal awarded by the University of Milan, Milan, Italy

1986        MERIT Award - National Institute of Mental Health

1995        Award from China Bureau of Foreign Experts Affairs, Suzhou Medical College, Suzhou, China as Outstanding Scientist

2000       Emeritus Professorship- Drexel University College of Medicine

2001      Drexel University College of Medicine established a Graduate Student Fellowship in his name.

2016       Ben & Sylvia Odesser Memorial Award, for Outstanding Contribution, Judaic Numismatics & Exonumia, awarded jointly by the Token and Medal Society and the American Israel Numismatic Association, Inc.

2016      NGL Award,  Small Club Publications for Best Article "Anti-Semitic Bigotry as Chronicled by Historical Medals", The Shekel, awarded by the Numismatic Literary Guild.

Scientific career
Institutions 1965-1966 Staff Fellow, Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, Bethesda, MD  (with Dr. B.B. Brodie)

1966-1968 Research Associate, Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY (with Dr. E. Costa)

1968-1971 Pharmacologist, Laboratory of Preclinical Pharmacology, National Institute of Mental Health, St. Elizabeths Hospital, Washington, DC

1971-1972 Chief, Section on Neuroendocrinology, National Institute of Mental Health, Washington, DC

1972-2000 Professor of Pharmacology, Medical College of Pennsylvania, Philadelphia, PA

1981-1982 Visiting Scientist, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy

1981-1998 Chief, Division of Neuropsychopharmacology, Medical College of Pennsylvania, Philadelphia, PA

1982 Visiting Scientist, Weizman Institute of Science, Rehovot, Israel

1983-2000 Professor of Psychiatry, Medical College of Pennsylvania, Philadelphia, PA

2000-Present    Emeritus Professor of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA.

Benjamin Weiss (January 26, 1937) is an American neuropharmacologist who is best known for his work with cyclic nucleotidephosphodiesterases.  He was the first to propose, based on his experimental work, that selective inhibition of phosphodiesterases which are expressed differentially in all tissues, could be used as a target for drug development. His work is the basis for many marketed and developmental human drugs that selectively inhibit cyclic nucleotide phosphodiesterases.

His investigations on the modulation of adrenergic responses in the pineal gland have resulted in the formation of new concepts that may explain the phenomena of drug tolerance and drug hypersensitivity.

He and his laboratory were also instrumental in the development of antisense oligonucleotides and antisense RNA as pharmacological tools to study calmodulin and dopamine receptors, and as pharmacological agents for antisense therapy in brain and other tissue.  

Weiss is also known for his extensive collection of historical and commemorativemedalsand has published several articles on the role commemorative medals play in religious and racial intolerance.


Early life and education[edit]

Weiss was born in The Bronxin 1937 and was raised on a chicken farm in New Jersey where his immigrant parents moved in 1946.  Weiss went to Toms RiverHigh School, graduating in 1954.  He received his undergraduate degree in Pharmacy (with Distinction) in 1958 and graduate education from the Philadelphia College of Pharmacy and Science (now, University of the Sciences), where he earned a M.Sc. in 1960 and a Ph.D. in Pharmacology in 1963, under the tutelage of G. Victor Rossi.  From 1963-1966 he had Postdoctoral Fellowship and a Staff Fellowship at the National Heart Institute, National Institute of Health, where he studied under Bernard B. Brodie.  He did further training as a Research Associate at Columbia University, College of Physicians and Surgeons, with Erminio Costafrom 1966-1968.  

Career[edit]

Scientific Career

Weiss edited two books: one on the potential therapeutic application of cyclic nucleotides: (Weiss, Benjamin, ed., Cyclic Nucleotides in Disease[1]), and another on the development and use of antisense oligonucleotides and antisense RNA as pharmacological tools and gene therapy (Antisense Oligodeoxynucleotides and Antisense RNA: Novel Pharmacological and Therapeutic Agents[2)).  He has also published over 300 scientific articles, reviews and abstracts on his research in the fields of Molecular Biology and Molecular Pharmacology.  In addition, he holds three patents on gene expression and antisense oligonucleotides directed to dopamine receptors and calmodulin.

From 1968 to 1972 Weiss worked at the National Institute of Mental Healthat St Elizabeths Hospital, Washington, D.C., where he held the position of Chief of the Section on Neuroendocrinology.  In 1972 he accepted the position of Professor of Pharmacologyat the Medical College of Pennsylvania (MCP), where he held the positions of Professor of Pharmacology and Psychiatry, and Chief of the Division of Neuropsychopharmacology.  He was also a Visiting Scientist at the Mario Negri Institute for Pharmacological Researchin Milan, Italy, and a Visiting Scientist at the Weizman Institute of Science in Israel. On retirement in 1999 he became an Emeritus Professor of Pharmacology and Psychiatry.  In 2002, when Drexel Universityassumed leadership of MCP, he was given the position of Emeritus Professor of Pharmacology and Physiology at Drexel University College of Medicine, the position he now holds.

Cyclic Nucleotide Phosphodiesterases: Starting at the National Institutes of Health and continuing at the Medical College of Pennsylvania (Now Drexel College of Medicine), Weiss and co-workers developed rapid phosphodiesterease assays [3, 4], separated different isozymes of phosphodiesterase in various tissues by electrophoretic methods [5,6]and  showed that drugs could  selectively inhibit the several isozymes of phosphodiesterase (link) isozymes.

Phosphodiesterase is an enzyme that breaks the phosphodiester bond in the cyclic moiety of cyclic AMP and cyclic GMP (https://en.wikipedia.org/wiki/Cyclic_nucleotide), which are second messengers used in intracellular signal transduction for a variety of hormones in cells.

He showed that a single cell type may contain more than one form of phosphodiesterase [6,7]. He also showed that different forms of phosphodiesterase could be induced or activated by certain neurohormones(e.g. norepinephrine) [7]and intracellular proteins (e.g. calmodulin) [8,9]. He demonstrated that there are different forms of phosphodiesterase in different tissues including the mammalian brain [5,6]and lung [10].

Weiss was the first to show that phosphodiesterase activity is altered in certain disease states [11,12, 13, 14, 15,16]and to propose that selective inhibition of phosphodiesterase could be the basis of drug selectivity [17,18,19,20].

Weiss and co-workers did extensive work which demonstrated that certain neuropeptides [21,22], alpha adrenergic antagonists [23]and phenothiazineantipsychotic drugs were potent inhibitors of calmodulin activated enzymes [24,25,26,27,28].

Calmodulin (https://en.wikipedia.org/wiki/Calmodulin) is a calcium-requiring enzyme that activates a variety of enzymes including kinases, phosphatases and phosphodiestereases. He proposed that one mechanism of action of antipsychotics drugs was through inhibition of calmodulin activated phosphodiesterase [8,9,27]. His laboratory’s studies on the binding of trifluoperazine and other phenothiazine antipsychotic agents to the calcium‑dependent activator of cyclic nucleotide phosphodiesterase (calmodulin) [17,18,19,20,26] have been extensively used to understand the biological actions of calmodulin.

Weiss is the father of the pharmaceutical field of phosphodiesterase drug inhibition, studies that have provided the basis for the development of a large number of commercially marketed drugs and experimental drugs across many therapeutic areas that have as their mechanism of action the selective inhibition of one or more isozymes of phosphodiesterase (PDE3; Phosphodiesterase inhibitor), including drugs for cardiac failure (Amrinone), Cilostazol)[1], asthma and stroke (PDE4; Ibudilast), psoriasis (PDE4; Apremilast), erectile dysfunction (PDE5; Sildenafil),[2], and schizophrenia (PFE4, PDE9; [3][4][5][6][7].

Modulation of Adrenergic Receptor-Linked Adenylate Cyclase System:  Using the pineal gland as a model, Weiss and his colleagues were the first to show that the beta-adrenergic receptor-linked adenylate cyclasesystem is modified chronically by a variety of physiological factors and pharmacological perturbations [reviewed in 29].

His laboratory demonstrated that this system is influenced by several physiological events: a) by sympathetic neuronal input, in that a long-term decrease in sympathetic input results in an increased responsiveness to adrenergic stimuli [30, 31]; b) by environmental lighting, in that darkness, which increased sympathetic input to the pineal gland decreases the response to adrenergic input[32]; by hormonal status in that low estrogen levels increase the responsiveness to norepinephrine[33]and c) by the age of the animal, in that older animals evidence a decrease in beta-adrenergic receptorsand a reduced response to adrenergic stimuli [34,35,36].  

Weiss showed additionally that the responses to adrenergic stimuli are also altered by a variety of pharmacological agents that chronically change adrenergic input.  For example, long term treatment with agents that reduce sympathetic input, like reserpine[37], 6-hydroxydopamine[38], guanethidine[39], and certain phenothiazine antipsychotic drugs [40]all increase the density of beta-adrenergic receptors and increase the responsiveness to adenylate cyclase.  By contrast,  treatment with drugs such as the anti-depressant desmethyimipramine, which increases adrenergic input, reduces the adrenergic receptors [41].These studies show that long-term changes that occur following physiological or pharmacological alterations in adrenergic input may be explained by a common biological principle:  that is, the degree to which an adrenergically-innervated structure can be stimulated is inversely related to the degree to which it had been previously stimulated. This hypothesis may provide a biochemical basis for explaining the altered responsiveness of the adrenergic system seen in aging and in males vs. females, and may explain the mechanism for drug supersensitivity and drug tolerance.

Antisense Oligonucleotidesand Antisense RNA:Weiss’ laboratory at the Department of Pharmacology, Medical College of Pennsylvania made discoveries on: 1) The role of calmodulin in neuronal differentiation and proliferation; 2) Behavioral and biochemical correlates of dopamineresponses in brain; 3) Development of antisense oligonucleotides and antisense RNA as pharmacological tools to study calmodulin and dopamine receptors, and as pharmacological agents for gene therapy in brain; and 4) Reversal of dopaminergic supersensitivity: preclinical mechanisms and clinical applications. 6) The studies laid the foundation for the therapeutic use of antisense oligonucleotides and antisense RNA in a variety of disease states.  More recent clinical studies by many others have, in fact, produced new types of antisense treatments, and a number of drugs are currently on the market and many others are in clinical development using the concept of antisense therapy, including incancer, Huntington’s Disease, and other Neurological diseases.

Weiss and his group, assisted by  Genoveva Uzunova (Davidkova), who carried out a significant part of the antisense RNA studies in his group, used molecular biological, biochemical, pharmacological, cell biological techniques (cell cultures, fluorescence microscopy), and mouse models, to develop antisense oligonucleotides to the D1 and D2 dopamine receptors. They were a leading group in the world in these studies and showed for the first time that intracerebroventricular (i.c.v.) and intrastriatal injection oligonucleotides targeted to the D1 or D2 dopamine receptor in mouse brain can block the biological effects of the targeted receptor with very high specificity  and, importantly, without inducing receptor supersensitivity, which is a significant drawback to the conventional neuroleptic drugs such as haloperidol[42,43,44].  Therefore, these novel pharmacological agents would not likely induce the debilitating motor side effects resulting from conventional pharmacological agents currently in use.

Since the effects of the oligonucleotides are relatively short-lasting (up to 2-3 days) and it is necessary to inject them repeatedly in mouse brain in order to achieve a long-term reduction in the D2 dopamine receptor mRNA and the dopamine receptor protein, and the concomitant long-term blockade of the behaviors modulated by these receptors, Weiss’ group developed a second approach – expression of D2 dopamine antisense RNA in brain by a non-viral plasmid vector. This approach was unique and the first to show that a single intrastriatal injection of D2dopamine receptor antisense RNA (targeted to the long isoform of the murine D2 dopamine receptor) can effectively block D2 dopamine-mediated behaviors for up to one month [45].  Moreover, this did not induce D2 receptor supersensitivity, unlike the conventional neuroleptic haloperidol, which blocks D2 dopamine receptors and several other subtypes of dopamine receptors [46]. These studies opened up the possibility to develop a new gene therapeutic approachto treat neurologic and psychiatric conditions associated with D2 receptor hyperactivity such as chorea and addiction to alcohol [47]. In a broader perspective, a similar gene therapeutic approach targeting other central nervous system (CNS) neuroreceptors and proteins may prove useful for treating other disorders of the CNS . The antisense RNA approach is an alternative to the RNA interference approach. RNA interference.

During this period, the studies of Weiss and his group were also focused on the use of antisense oligonucleotides [48]and antisense RNA expression vectors to calmodulin [49]  ,which is a ubiquitous calcium binding protein in brain encoded by three different genes that give rise to several transcripts. These studies helped to elucidate the essential role of calmodulin in the proliferation and differentiation of nerve cells and suggest a novel approach with the potential for gene therapy of tumors that express high levels of calmodulin, such as gliomas and certain forms of breast cancer. Previously it has been proposed that pharmacological targeting of calmodulin is useful in treatment of cancer [50,51]. However, it is conceivable that use of an antisense approach will be more specific and less toxic than the typical cancer chemotherapeutic drugs.

Medal Collecting Career

Weiss was first introduced to the field of medal collecting in 1972 by one of his postdoctoral fellows, Robert Levin. Following his retirement from his career as a Neuropharmacologist in 2000, Weiss has been devoting much of his time collecting and studying the art and history of historical and commemorative medals, a portion of which are on display at the Philadelphia Museum of Art, and which are fully described on the website, Historical and Commemorative Medals.

Weiss has also been writing articles on the role medals play in religious and racial bigotry, for which he has received awards from the Numismatic Literary Guildand a medal issued jointly by the Token and Medal Societyand theAmerican Israel Numismatic Association.  Beginning in 2007 he served for ten years as the Webmaster of the Medal Collectors of Americawebsite, and is currently a Juror for the American Medallic Sculpture Association, and a Board Member of the Medal Collectors of America.  

Honors and awards[edit]

From the Philadelphia College of Pharmacy and Science, Weiss received a Gold Medal for attaining the Highest Scholastic Average of College Graduates, the Joseph W. E. Harrison Gold Medal for Excellence in Pharmacology, the Frederick William Haussman Memorial Prize, the Dobbins Scholarship, Rexall Award, and Borden Award.  While at the Medical College of Pennsylvania he received the Christian R. and Mary F. Lindback Award for Distinguished Teaching. In 1987, he received a MERIT Award from the National Institute of Mental Health. He also received a Research Medal awarded by the University of Milan, Milan, Italy, and an Outstanding Scientist Award from the China Bureau of Foreign Experts Affairs, Suzhou, China. In 1981, he was named by the Institute for Scientific Information as one of the Top One Thousand Most Quoted Contemporary Scientists in the World.

In 2001, Drexel University College of Medicine established a Graduate Student Fellowship in his name.

Personal Life [edit]

Weiss was the youngest of three sons of Harry Weiss, who emigrated from Austria in 1921, and Pauline Weiss (nee Feinberg), born in Poland and who came to the United States in 1921.  His father had a laundry business in New York and later owned a chicken farm in Toms River, New Jersey.  His brothers were Lester Weiss, a noted pediatric physician and geneticist, who worked at Henry Ford Hospital in Detroit, Michigan, and Howard Weiss, a pharmacist and community organizer, advocating for housing for low income residents in Brooklyn, New York.

In 1959 Weiss married Joyce Zelnick.  They have three children and five grandchildren.

In addition to collecting medals and working on his personal website, Weiss now spends his time woodworking, gardening, engaging in various other crafts, and enjoying his grandchildren. He also writes stories about his boyhood, growing up in a tenement in The Bronx and on a chicken farm in Toms River.  He graduated from Toms River High School in 1954.

In 1959 Weiss married Joyce Zelnick.  They have three children and five grandchildren.

Trainees:[edit]

Weiss trained a number of Graduate Students and Postdoctoral Fellows.  These include:

Bai, Guang, M.D., Ph.D. (Research Assistant Professor, University of Maryland School of Dentistry)

[8]

[9]

Cantor, Elinor H. “Ellie”, Ph.D., MBA (Adjunct Faculty, Department of Pharmacology, Drexel University College of Medicine)

[10]

Chen, Jiang Fan, M.D., Ph.D. (Professor of Neurology & Pharmacology, Boston University School of Medicine)

[11]

Cimino, Mauro (Professor, Department of Biology, University of Milan, Milan, Italy)

[12]

Clark, M. Blair, Ph.D. (Assistant Professor, Department of Anatomy, University of Maryland)

Earl, Craig Q., Ph.D. (Executive Director, Project Delivery at PRA Health Sciences)

[13]

Ebadi, Manuchair “Mike”, Ph.D., deceased, (formerly Professor and Chairman, Department of Pharmacology, University of Nebraska Medical Center; Chester Fritz Distinguished Professor, Associate Vice President for Health Affairs at Und, Associate Dean for Research and Program Development, and Director of the Center for Excellence in Neurosciences at the Und School of Medicine and Health Sciences)

[14]

[15]

Clark, M. Blair Clark, Ph.D., (Assistant Professor, Department of Anatomy, University of Maryland

School of Medicine)

Fertel, Richard, Ph.D. (Emeritus Associate Professor Department of Pharmacology, University of Ohio)

[16]

Greenberg, Louise H., Ph.D. (Retired Visiting Assistant Professor, Department of Pharmacology, Medical College of PA)

[17]

Hait, William N., M.D., Ph.D. (Global Head, Johnson & Johnson External Innovation)

[18]

[19]

Hao, Wangfang Hao, M.Sc. (Johnson and Johnson Research Laboratories)

Kidman, Antony, Ph.D., deceased (Formerly at The University of Technology, Sidney, Australia; father of actress Nicole Kidman)

Antony Kidman

Levin, Robert, Ph.D. (Professor Emeritus, Department of Pharmaceutical Sciences, ACPHS; Research Career Scientist, Stratton VA Medical Center)

[20]

[21]

Natsukari, Naoki, M.D., Ph.D.

[22]

[23]

Prozialeck, Walter C., Ph.D. (Chairman, Department of Pharmacology, Chicago College of Osteopathic Medicine)

[24]

Qin, Zheng-Hong, M.D. (Professor, Soochow University, Suzhou, China)

[25].

[26]

Sellinger-Barnette, Mary, Ph.D. (Director and Head, Clinical Research Group, IOC DPU, Cancer Research, GSK, Retired)

[27]

Strada, Samuel J., Ph. D. (Dean Emeritus, University of South Alabama College of Medicine)

[28]

Thermos, Kyriaki, Ph.D. (Professor and Chair, Department of Pharmacology; Director, Graduate Program of Neurosciences School of Medicine, University of Crete , Heraklion, Crete, Greece)

[29]

Uzunov, Petko, M.D., deceased (Former Professor and Chairman, Department of Pharmacology; President, Bulgarian Medical Academy, Sofia, Bulgaria)

[30]

Uzunova (Davidkova), Genoveva, M.D., Ph.D. (Fellow in Syndromal Autism and Orphan Diseases at Albert Einstein College of Medicine/ Montefiore Medical Center)

[31]

Wallace, Thomas L., Ph.D. (Senior Medical Science Liaison, Genentech)

[32]

Winkler, James, Ph.D. (Chief Scientific Officer, Arvinas, Inc.; Drug Discovery and Development Consultant, James D Winkler LLC, Consulting)

[33]

References[edit]

1. Weiss, B.: Editor, Cyclic Nucleotides in Disease, University Park Press, Baltimore, MD. 1975.

2. Weiss, B.: Editor: Antisense Oligodeoxynucleotides and Antisense RNA: Novel Pharmacological and Therapeutic Agents CRC Press, Boca Raton, FL. 1997.

3.Weiss B, Lehne R, Strada S. Rapid microassay of adenosine 3',5'-monophosphate phosphodiesterase activity. Anal Biochem. 1972 Jan;45(1):222-35. PubMed PMID: 4333123.

4. Fertel R, Weiss B.: A microassay for guanosine 3',5'-monophosphate phosphodiesterase activity. Anal Biochem. 1974 Jun;59(2):386-98. PubMed PMID: 4365804.

5. Uzunov, P. and Weiss, B.: Separation of multiple molecular forms of cyclic adenosine 3',5'‑monophosphate phosphodiesterase in rat cerebellum by polyacrylamide gel electrophoresis. Biochim. Biophys. Acta 284:220‑226, 1972.

6. Uzunov, P., Shein, H.M. and Weiss, B.: Multiple forms of cyclic 3',5'‑AMP phosphodiesterase of rat cerebrum and cloned astrocytoma and neuroblastoma cells. Neuropharmacology 13:377‑391, 1974.

7. Uzunov, P., Shein, H.M. and Weiss, B.: Cyclic AMP phosphodiesterase in cloned astrocytoma cells: norepinephrine induces a specific enzyme form. Science 180:304‑306, 1973.

8. Weiss, B., Prozialeck, W., Cimino, M., Barnette, M.S. and Wallace, T.L.: Pharmacological regulation of calmodulin. In: Calmodulin and Cell Functions, Ann. N.Y. Acad. Sci. 356:319‑345, 1980.

9. Weiss, B., Prozialeck, W.C. and Wallace, T.L.: Interaction of drugs with calmodulin: Biochemical, pharmacological and clinical implications. Biochem. Pharmacol. 31:2217‑2226, 1982.

10. Fertel, R. and Weiss, B.: Properties and drug responsiveness of cyclic nucleotide phosphodiesterases of rat lung. Mol. Pharmacol. 12:678‑687, 1976. Hait, W.N. and Weiss, B.: Increased cyclic nucleotide phosphodiesterase activity in leukemic lymphocytes. Nature 259:321‑323, 1976.

11. Hait, W.N. and Weiss, B.: Characteristics of the cyclic nucleotide phosphodiesterases of normal and leukemic lymphocytes. Biochim. Biophys. Acta 497:86‑100, 1977.

12. Hait, W.N. and Weiss, B.: Increased cyclic nucleotide phosphodiesterase activity in leukemic lymphocytes. Nature 259:321‑323, 1976.

13. Levin, R.M. and Weiss, B.: Characteristics of the cyclic nucleotide phosphodiesterases in a transplantable pheochromocytoma and adrenal medulla of the rat. Cancer Res. 38:915‑920, 1978.

14. Weiss, B. and Winchurch, R.A.: Analyses of cyclic nucleotide phosphodiesterases in lymphocytes from normal and aged leukemic mice. Cancer Res. 38:1274‑1280, 1978.

15. Winchurch, R., Hait, W. and Weiss, B.: Cyclic AMP phosphodiesterase activity of murine T and

B lymphocytes. Cell. Immunol. 41:421‑426, 1978.

16. Hait, W.N. and Weiss, B.: Cyclic nucleotide phosphodiesterase of normal and leukemic lymphocytes: kinetic properties and selective alteration of the activity of the multiple molecular forms. Mol. Pharmacol. 16:851‑864, 1979.

17. Levin, R.M. and Weiss, B.: Mechanism by which psychotropic drugs inhibit adenosine cyclic 3',5'‑monophosphate phosphodiesterase of brain. Mol. Pharmacol. 12:581‑589, 1976.

18. Levin, R.M. and Weiss, B.: Binding of trifluoperazine to the calcium‑dependent activator of cyclic nucleotide phosphodiesterase. Mol. Pharmacol. 13:690‑697, 1977. (a)

19. Levin, R.M. and Weiss, B.: Selective binding of antipsychotics and other psychoactive agents to the calcium‑dependent activator of cyclic nucleotide phosphodiesterase. J. Pharmacol. Exp. Ther. 208:454‑459, 1979.

20. Levin, R.M. and Weiss, B.: Specificity of the binding of trifluoperazine to the calcium‑dependent activator of phosphodiesterase and to a series of other calcium‑binding proteins. Biochim. Biophys. Acta 540:197‑204, 1978. (b)

21. Sellinger‑Barnette, M. and Weiss, B.: Interaction of beta‑endorphin and other opioid peptides with calmodulin. Mol. Pharmacol. 21:86‑91, 1982.

22. Barnette, M.S. and Weiss, B.: Interaction of neuropeptides with calmodulin. A structure‑activity study. Psychopharmacol. Bull., 19:387‑392, 1983.

23. Earl CQ, Prozialeck WC, Weiss B.: Interaction of alpha adrenergic antagonists with calmodulin. Life Sci. 1984 Jul 30;35(5):525-34. PubMed PMID: 6146911.

24. Weiss, B. and Hait, W.N.: Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents. Ann. Rev. Pharmacol. Toxicol. 17:441‑477, 1977.

25. Weiss, B. and Levin, R.M.: Mechanism for selectively inhibiting the activation of cyclic nucleotide phosphodiesterase and adenylate cyclase by antipsychotic agents. Adv. Cycl. Nucl. Res. 9:285‑304, 1978.

26. Prozialeck, W.C. and Weiss, B.: Inhibition of calmodulin by phenothiazines and related drugs; structure‑activity relationships. J. Pharmacol. Exptl. Therap. 222:509‑516, 1982.

27. Weiss, B., Earl, C. and Prozialeck, W.C.: Biochemical and possible neuropsychopharmacological implications of inhibiting calmodulin activity. Psychopharmacol. Bull., 19:378‑386, 1983.

28. Weiss, B., Prozialeck, W.C. and Roberts‑Lewis, J.M.: Development of selective inhibitors of calmodulin‑dependent phosphodiesterase and adenylate cyclase; in Design of Enzyme Inhibitors as Drugs, ed. M. Sandler and H.J. Smith, Oxford University Press, New York, pp. 650‑697, 1989.

29. Weiss, B., Greenberg, L.H. and Clark, M.B.: Physiological and pharmacological modulation of the beta-adrenergic receptor-linked adenylate cyclase system: supersensitivity and subsensitivity. In: Dynamics of Neurotransmitter Function, ed. I. Hanin, Raven Press, New York, pp. 319-330, 1984.

30. Weiss, B. and Costa, E.: Adenyl Cyclase activity in rat pineal gland: Effects of chronic denervation and norepinephrine. Science 156:1750-1752, 1967.

31. Strada, S.J. and Weiss, B.: Increased response to catecholamines of the cyclic AMP system of rat pineal gland induced by decreased sympathetic activity. Arch. Biochem. Biophys. 160:197- 204, 1974.

32. Weiss, B.: Effects of environmental lighting and chronic denervation on the activation of adenyl cyclase of rat pineal gland by norepinephrine and sodium fluoride. J. Pharmacol. Exp. Ther. 168:146-152, 1969.

33. Weiss, B. and Crayton, J.: Gonadal hormones as regulators of pineal adenyl cyclase activity. Endocrinology 87:527-533, 1970.

34. Greenberg, L.H., Dix, R.K. and Weiss, B.: Age-related changes in the binding of dihydroalprenolol in rat brain. In: Pharmacological Intervention in the Aging Process, eds. J. Roberts, R.C. Adelman and V.J. Cristofalo, Plenum Press, New York, pp. 245-249, 1978.

35. Greenberg, L.H. and Weiss, B.: Beta adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity. Science 201:61-63, 1978.

36. Weiss, B., Greenberg, L.H. and Cantor, E.: Denervation supersensitivity and beta-adrenergic receptors as a function of age. In: Receptors for Neurotransmitters and Peptide Hormones, eds. G. Pepeu, M.J. Kuhar and S.J. Enna, Raven Press, New York, p 461-472, 1980.

37. Greenberg, L.H. and Weiss, B.: Ability of aged rats to alter beta-adrenergic receptors of brain in response to repeated administration of reserpine and desmethylimipramine. J. Pharmacol. Exp. Ther. 211:309-316, 1979.

38. Strada, S.J., Uzunov, P. and Weiss, B.: Increased sensitivity to norepinephrine (NE) of the cyclic 3',5'-AMP (cAMP) system of rat brain following 6-hydroxydopamine (6-HDM). Pharmacologist 13:257, 1971.

39. Glaubiger, G., Tsai, B.S., Lefkowitz, R.J., Johnson, E.M., Jr. and Weiss, B.: Chronic guanethidine treatment increases cardiac beta-adrenergic receptors. Nature 273:240-242, 1978.

40. Weiss, B. and Greenberg, L.H.: Modulation of beta-adrenergic receptors and calmodulin following acute and chronic treatment with neuroleptics. In: Adv. Biochem. Psychopharmacol., Vol. 24 - Long-Term Effects of Neuroleptics, eds. F. Cattabeni, G. Racagni, P.F. Spano and E. Costa, Raven Press, New York, pp. 139-146, 1980.

41. Moyer, J.A., Greenberg, L.H., Frazer, A., Brunswick, D.J., Mendels, J. and Weiss, B.: Opposite effects of acute and repeated administration of desmethylimipramine on adrenergic responsiveness in rat pineal gland. Life Sci. 24:2237-2244, 1979.

42. Weiss, Benjamin; Long-Wu, Zhou; Zhang, Sui-Po; Qin Z-H. (1993). “Antisense oligodeoxynucleotide inhibits D2 dopamine receptor-mediated behavior and D2 messenger RNA” Neuroscience55(3): 607-612. [34]: 8413923

43. Zhang, Sui-Po; Long-Wu, Zhou; Weiss, Benjamin (1994). “Oligodeoxynucleotide to the D1 dopamine receptor mRNA inhibits D1 dopamine receptor-mediated behaviors in normal mice and in mice lesioned with 6-hydroxydopamine” J. Pharmacol. Experimental Ther.271(3): 1462- 1470. PMID: 7996459

44. Weiss, Benjamin; Zhang, Sui-Po; Zhou, Long-Wu (1997) “Antisense strategies in dopamine receptor pharmacology” Life Sciences60(7): 433-455. doi.org/10.1016/S0024-3205(96)00566-8PMID: 9042372

45. Weiss, Benjamin; Davidkova, Genoveva; Zhou, Long-Wu, Zhang, Sui-Po, Morabito, Mark (1997). “Expression of a D2 dopamine receptor antisense RNA in brain inhibits D2-mediated behaviors” Neurochemistry International31(4): 571-580. doi.org/10.1016/S0197-0186(97)00025-9PMID: 9308007

46. Davidkova, Genoveva; Zhou, Long-Wu; Morabito, Mark; Zhang, Sui-Po; Weiss, Benjamin (1998). “D2 dopamine antisense RNA expression vector, unlike haloperidol, produces long-term inhibition of D2 dopamine-mediated behaviors without causing up-regulation of D2 dopamine receptors” J. Pharmacol. Exper. Therapeutics 285(3): 1187-1196. [35] PMID: 9618422

47. Weiss, Benjamin; Davidkova, Genoveva; Zhou, Long-Wu (1999).”Antisense RNA gene therapy for studying and modulating biological processes” Cell Mol. Life Sci.55(3): 334-358. DOI: 10.1007/s000180050296PMID: 10228554

48. Hou, Wang-Fang; Zhang, Sui-Po; Davidkova, Genoveva; Nichols, Robert; Weiss, Benjamin (1998) “Effects on antisense oligonucleotides directed to individual calmodulin gene transcripts on the proliferation and differentiation of PC12 cells” Antisense Nucleic Acids Drug Dev. 8(4): 295-308.DOI: 10.1089/oli.1.1998.8.295PMID: 9743467

49. Davidkova, Genoveva; Zhang, Sui-Po; Nichols, Robert; Weiss, Benjamin (1996) “Reduced level of calmodulin in PC12 cells induced by stable expression of calmodulin antisense RNA inhibits cell proliferation and induces neurite outgrowth” Neuroscience75(4): 1003-1019.doi.org/10.1016/0306-4522(96)00230-8PMID: 8938737

50. Hait, W.N. and Lazo, J.S.: Calmodulin: a potential target for cancer chemotherapeutic agents. J. Clin. Oncol. 4:994-1012, 1986.

51. Mayur, Y.C., Jagadeesh, S. and Thimmaiah, K.N.: Targeting calmodulin in reversing multi drug resistance in cancer cells. Mini Rev. Med. Chem. 6:1383-1389, 2006.

References Related to Medal Collecting [edit]

Weiss, Benjamin, Badge of Intolerance, The Numismatist, vol. 124, no. 5: 48-51, 2011.

Weiss, Benjamin,  Medallic History of the War of 1812:  Consequences to the American Indian Nations,  Journal of the Medal Collectors of America (MCA Advisory), Vol.15, No. 5, Sept-Oct  pp. 1-32, 2012.

Weiss, Benjamin, Medallic History of the War of 1812: Catalyst for Destruction of the American Indian Nations  (e-book)  Artwis.com,  Kuntstpedia Foundation, The Netherlands, 2013.

Weiss, Benjamin, Medallic History of Religious and Racial Intolerance:  Medals As Instruments For Promoting Bigotry   Oral Presentation at Villanova University  2013.

Weiss, Benjamin, Medals of the Glorious Revolution: The Influence of Catholic-Protestant Antagonism, ANS Magazine, Vol. 13, Issue 1, pp. 6-23. American Numismatic Society, New York, 2014.

Weiss, Benjamin,  Anti-Semitic Bigotry: A Retrospective As Chronicled by Commemorative Medals, (e-book)  Artwis.com, Kunstpedia Foundation, The Netherlands, 2015.

Weiss, Benjamin, Anti-Semitic Medals Through History: Anti-Semitic Bigotry as Chronicled by Historical Medals, Part I.  The Shekel: Journal of Israel and Jewish History and Numismatics, Vol. 48, No. 1, pp. 12-48, 2015.

Weiss, Benjamin, Anti-Semitic Medals Through History: Anti-Semitic Bigotry as Chronicled by Historical Medals, Part II. The Shekel: Journal of Israel and Jewish History and Numismatics, Vol. 48, No. 2, pp. 6-25, 2015.

Weiss, Benjamin, Anti-Semitic Medals Through History: Anti-Semitic Bigotry as Chronicled by Historical Medals, Part III, Conclusion. The Shekel: Journal of Israel and Jewish History and Numismatics, Vol. 48, No. 3, pp. 6-35, 2015.

Weiss, Benjamin, Anti-Semitic Medals Through History: Anti-Semitic Bigotry as Chronicled by Historical Medals, Jewish-American Hall of Fame, Jewish Museum in Cyberspace, 2015.

Weiss, Benjamin, Medals as Instruments for Promoting Anti-Semitic Bigotry,   Artwis.com, Kunstpedia Foundation, The Netherlands, 2015.

Weiss, Benjamin,  How a German Became King of England: Part I: A Medallic History of Religious Conflicts in Britain, Journal of the Medal Collectors of America (MCA Advisory), Vol.19, No. 2, pp. 12-26, 2016.

Weiss, Benjamin, How a German Became King of England: Part II:  Hanoverian Dynasty Incites Jacobite Rebellions, Journal of the Medal Collectors of America (MCA Advisory), Vol.19, No. 3, pp. 8-19, 2016.

Weiss, Benjamin, Medal Commemorating the Visit of Sultan Abdul Aziz to London, Revisited,  Journal of the Medal Collectors of America (MCA Advisory), Vol, 20, No. 2, pp.16-23, 2017.


External links[edit]

References[edit]

  1. "CV Pharmacology | Phosphodiesterase Inhibitors".
  2. "CV Pharmacology | Phosphodiesterase Inhibitors".
  3. https://www.boehringer-ingelheim.com/PDE9-Inhibition-in-AD
  4. Snyder, G. L.; Vanover, K. E. (2017). "PDE Inhibitors for the Treatment of Schizophrenia". Advances in Neurobiology. 17: 385–409. doi:10.1007/978-3-319-58811-7_14. ISBN 978-3-319-58809-4. PMID 28956340.
  5. Heckman, P. R.; Van Duinen, M. A.; Bollen, E. P.; Nishi, A.; Wennogle, L. P.; Blokland, A.; Prickaerts, J. (2016). "Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications". The International Journal of Neuropsychopharmacology. 19 (10): pyw030. doi:10.1093/ijnp/pyw030. PMC 5091819. PMID 27037577.
  6. https://clinicaltrials.gov/ct2/show/NCT01813955
  7. Halene, Tobias B.; Siegel, Steven J. (2007). "PDE inhibitors in psychiatry–future options for dementia, depression and schizophrenia?". Drug Discovery Today. 12 (19–20): 870–878. doi:10.1016/j.drudis.2007.07.023. PMID 17933689.
  8. "Dr. Bai".
  9. https://www.umaryland.edu/cacpr/cacpr-membership/executive-committee-and-faculty-members-information/guang-bai-md-phd/
  10. https://www.linkedin.com/in/ellie-cantor-93776a2/
  11. http://www.bumc.bu.edu/neurology/clinicalfaculty/jiang-fan-chen-md-phd/
  12. http://www.disfeb.unimi.it/ecm/home/ricerca/laboratori-ricerca/laboratorio-di-farmacologia-della-trombosi-e-aterosclerosi/mauro-cimino
  13. https://www.linkedin.com/in/craig-earl-95945b10/
  14. "Remembering Manuchair "Mike" Ebadi | UND University Letter".
  15. "Remembering Manuchair (Mike) Ebadi, Ph.D. | UNMC".
  16. https://www.researchgate.net/scientific-contributions/39198420_Richard_H_Fertel
  17. "Veiligheidscontrole nodig".
  18. "William N. Hait | JNJ Innovation".
  19. https://www.linkedin.com/in/williamhait/
  20. https://www.researchgate.net/profile/Robert_Levin3
  21. https://www.researchgate.net/profile/Robert_Levin5
  22. "Naoki Natsukari".
  23. https://www.researchgate.net/scientific-contributions/2012745331_Naoki_Natsukari
  24. https://www.midwestern.edu/prozialeck.html
  25. "Bloomberg - Are you a robot?".
  26. https://www.researchgate.net/scientific-contributions/38819685_Zheng-Hong_Qin
  27. https://www.linkedin.com/in/mary-barnette-24835a9/
  28. https://www.linkedin.com/in/samuel-strada-05986617/
  29. http://www.english.med.uoc.gr/sites/all/arxeia/cv/cv-thermos-kyriaki_en.pdf
  30. "Communitas Foundation - JCM vol. 2, issue 2, 2009 -".
  31. https://www.linkedin.com/in/genoveva-uzunova-m-d-ph-d-5917261b/
  32. https://www.linkedin.com/in/thomas-wallace-5a48679/
  33. https://www.linkedin.com/in/james-winkler-52291835/
  34. https://doi.org/10.1016/0306-4522(93)90426-GPMID
  35. Weiss, Benjamin; Zhang, Sui-Po; Morabito, Mark; Zhou, Long-Wu; Davidkova, Genoveva (June 1998). "D2 Dopamine Antisense RNA Expression Vector, Unlike Haloperidol, Produces Long-term Inhibition of D2Dopamine-Mediated Behaviors without Causing Up-regulation of D2 Dopamine Receptors". Journal of Pharmacology and Experimental Therapeutics. 285 (3): 1187–1196.


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