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Product Design

Nicotine Receptor Program - University of Rochester

Date: 21 Mar 1980
Length: 3 pages
1000127786-7788
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Abstract

States Dr. Leo Abood's work with the Research Center provides valuable insight to nicotine research, assists with the Behavioral Research Group, interprets test results, supplies current information on nicotine pharmacology and sets up binding assays for nicotine analogues. Indicates critical importance of the "prostation syndrome" test as "it is the first biological response to nicotine that does not appear to be mediated by a cholinergic receptor.", states the need to ascertain seperation of peripheral and central effects, and to design a nicotine analogue that has CNS activity with little or no peripheral effects. Cites the need to determine the receptor is non-cholinergic and what role the "prostration syndrome" plays in smoker psychology. Indicates collaboration with German researchers has been of highest quality, but minimal with assistance. Underscores Dr. Abood's status in understanding the neuropharmacological aspects of nicotine and that he has obtained a "purified nicotinic receptor from Torpedo", and established a binding assay. Says the assay will diffentiate compounds that bind to the nicotine receptor and activate it, and those that do not, thus giving a clearer understanding of the nicotine receptor.

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Notes

Main Entry: cho·lin·er·gic Pronunciation: "kO-l&-'n&r-jik Function: adjective Etymology: International Scientific Vocabulary Date: 1934 1 : liberating, activated by, or involving acetylcholine 2 : resembling acetylcholine especially in physiologic action - cho·lin·er·gi·cal·ly /-ji-k(&-)lE/ adverb [Merriam-Webster]

Author
Sanders, Edward B. (Ted), Ph.D. (PM Dir. of Chemical Research)
Neuchatel, '99
Recipient
Seligman, Robert B. (PM VP of R&D c. 1976-82)
Vice President of Research and Development at Philip Morris Richmond, VA 1976-1982. Reported to Senior Vice President of Operations. In 1982 transferred to tobacco technology group. Wanted to share ammonia and other tobacco technology with PM International companies.
Dunn, William L., Jr. (PM Smoker Psychology Principal Scientist 1970s-80s)
Principal scientist at PM during the 1970s and 1980s, nicknamed the "Nicotine Kid." Supervised Victor DeNoble, Paul Mele, Carolyn Levy and others. Led "smoker psychology" programs for PM.
Charles, James L., Ph.D. (PM, R&D VP, Pharmacologist, Industry Expert)
Vice President of Research and a scientist for Philip Morris, Inc. Vice President of Research for Philip Morris, Inc. in 1986 and then again from 1992 to 1993.
Seeman, Jeffrey I., Ph.D. (PM scientist -- nicotine analogs)
Defense
Hypothesis
Behavior Targeting
Cigarette's effect of enhancing/mitigating specific behaviors
Health effects
Design changes which have measurably altered health effects of cigarette smoke, both for smokers and nonsmokers.
Measuring human intake
Development of scientifically valid procedures for measuring tar and nicotine levels that more accurately reflect human intake.
Nicotine transport, transfer, and uptake
Design changes which alter nicotine delivery or effect how the product causes and maintains dependence, including transfer of nicotine from tobacco to smoke, and uptake into the body.
Free Nicotine
Neurobiology
Keyword
Adrenal effects
Blood nicotine
Brain activity
Behavioral effects (Behavioral pharmacology)
Addiction behavior, withdrawal, and measured nicotine effects
Central nervous system (CNS)
Drug effects
Neuropharmacology (Electrophysiology)
Receptor, brain, and CNS effects (EEG, trigeminal response, etc.)
Nicotine delivery (Smoke nicotine or nicotine yield)
Physiological effects
Receptors
Smoke Constituent
Nicotine
Design Component
Nicotine content (Tobacco nicotine content)
Total nicotine in the unburnt tobacco rod
Nicotine transfer efficiency (NTE)
Named Organization
Research Center
University of Rochester
Behavioral Research Group
Subject
CNS/Brain (Effects)
Experimental Technology (Technology)
Formulas (Design)
nicotine technology
nicotine analogues (Technology)
Receptors (Effects)
Smoke Nicotine (Measures)
Test/Smoke Constituents (Testing)

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PHILIP MORRIS U. S. A. 1 tlTER-OFF I CE CORRESPONDEMI CE RICHMOND. YIRGtNIA .subjest: . Nicotine Receptor Program - University of Rochester Dr. Leo Abood's collaboration with the Research. Center has been extremely beneficial to the nicotine program. His . namely, assistance has impinged on four different areas; direct assistance to the Behavioral Research Group, assistance in interpreting peripheral testing results, providing us with current information regarding work concerning nicotine pharmacology at other locations, and direct hands on work in setting up binding assays for nicotine analogues.synthes-ized by members of Charge Number 2500. Dr. Abood's interaction with the Behavioral Research Group has been of crucial importance in establishing the "prostrati.on syndrome" test. The value of this particular technique to the nicotine program cannot be overstated in that i.t is the first biological response to nicotine that does not appear to be mediated by a cholinergic receptor. The original charge of the nicotine program was Cl) to ascertain if the central and peripheral effects could be "separated" and C2) to design a nicotine analogue which would have CNS activity equivalent to nicotine with little or no peripheral effect. Since it has been well-established that nicotine's peripheral effects are cholinergic, the discovery of a non,cholinergic central recep- tor provides us withn reason to believe in the ultimate success of the program. Future work involving the "prostration syndrome" must unequivocally establish the non-cholinergic nature of the receptor and must explore the role that the "prostration syndrome" receptor plays inthe psychology of smoking. Leo's expertise, involving his experience in the necessary methodology as well as his work in attempting to characterize the natural neurotransmitter for this receptor, is crucial to the vigorous prosecution of this work. For several years we have been receiving data on peripheral $ screening of our nicotine analogues from Germany. The quality 0 of the work has been consistently of the highest calibre. On O the other hand, the German laboratory has been of minimal assis~ tance regarding interpretation. The problem is a combination N of our lack of pharmacological sophistication coupled with the q large distance between Richmond and Cologne. We have existed q with this problem for some time since it would be virtually Qy impossible to match the good service we are getting elsewhere. C? Leo Abood's association with Philip Morris has consequently filled a void. Not only have we been able to get a better
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~=interesting follow-up tests on certatin analogues as well. handle on both the meaning of a given~ test result but possible . B. Seligman, -2- March 21, 1980 Dr. Abood has occupied a position of preeminence in neuropharmacology for some time, Consequently,. he has contacts receptor but do not activate it and those compounds which do not bind. With this information we hope to get a clearer pic- ture of the nicotinic receptor. us to differentiate between compounds which bind to the nicotinic .of sending out the first set of compounds. This assay will allow Torpedo and has established the experimental conditions for -assaying binding to the receptor. We are now in the process Leohas obtained a sample of purified nicotinic receptor from . -us in carrying out binding assays for our synthetic analogues. ~-' of the latter involves the direct assistance Leo~ is providing us, developments as well as in more direct ways. The best example ~ have benefitted us by keeping us abreast of interesting current '' of nicotine pharmacology, throughout the country. These contacts witn virtually ail of the laboratories working on various aspects In summary, I feel that we have benfitted considerably ,from Leo's association with the Research Center, and I trust that this association will continue. cc: 'Dr. T. S. Osdene Dr. Mr. Dr. W. J. J. L. L. I. Dunn Charles Seeman ea.
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t t~rrt 21 W-W ~, S. OSDENE

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