Product Design
Subject: Testing of Nicotine Analogues
Abstract
Offers suggestions for reference materials regarding nicotine analogues in order to get testing under way more quickly. States that due to the number of compounds "of interest to us," full-scale testing cannot be undertaken, but "sufficient information can be derived from three specific tests": 1) effect of nicotine analogues on frog rectus-abdominus muscle; 2) effect of nicotine analogues on contraction of "the isolated guinea pig ileum"; and 3) the effect of nicotine analogues on the cat's blood pressure. Offers a list of written studies to accompany each test. Appends a list of additional compounds which will be tested. Same as Bates #1000053956. Appendix is not included.
Fields
- Notes
Lipper, S. Pelikan, E.W. Lundgren, G. Bolmstedt, B. Nanivadekar, A.S. Gaitonde, B.B Bogdanovic, S.B. Rakic, M.M Beleslin, D.B. Ng, K.K.F. Curtis, D.R. Ryall, R.W. Clark, M.S.G. Rand, M.J. Vanov, S. Cowan, F.F. Greene, L.H. Share, N.N. Melville, K.F. Gebber, G.L.
- Author
- Sanders, Edward B. (Ted), Ph.D. (PM Dir. of Chemical Research)Neuchatel, '99
- Recipient
- Gannon, Walter F.Manager Gapsis
- Osdene, Thomas Stefan, Ph.D. (Director of Science and Technology, Philip Morris [1986])
Ph.D. in Organic Chemistry. Ten years of research when he started with PM in 1965. Worked in Chemical Research Division of PM 1965-66; Chemical and Biological Research Division 1966-69; Director of Research 1969-1984, also assumed independent position as Director of Research and Extramural Studies during these years; became Director of Science and Technology in 1984, reporting directly to Philip Morris USA Executive VP Mark Serrano. Involved with Center for Indoor Air Research (CIAR) 1988. Attended PM's Operation Downunder Conference in June, 1987. Retired 1993. - Osdene, Thomas Stefan, Ph.D. (Director of Science and Technology, Philip Morris [1986])
- Keyword
- Pharmacologist
- Annales of the NY Academyy of Science
- Arch. Int. Pharmacodyn.
- British Journal of Pharmacology
- Experimental Brain Research
- Animal research
- Physiological effects
- Nicotine
- Annales of the NY Academyy of Science
- Additive
- Nicotine
- Nicotine analogues
- Smoke Constituent
- Nicotine
- Subject
- nicotine analogues (Technology)
Document Images
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PHILIP MORRIS
U.S.A.
INTER-OFFICE CORRESPONDENCE
RICHMOND, VIRGINIA
70: , Dr. W. F. Gannon Date: January 31, 1974
From: . E. B. Sanders~
Subject: . Testing of Nicotine Analogues.
other two tests which we suggest). Three other papers of interest
for this Ya2'tici.iiai test are :
1. S. Lipper and E. W. Pelikan, Pharmacologist, 8, 188 (1966).
2. S. Lipper and E. W~. Pelikan, Pharmacologist, 9, 226 (1967).
3. B. Holmstedt and G. Lundgren, Ann. N.Y. Acad. Sci., 142,
In order to expedite testing of nicotine analogues, we would
like to offer several suggestions as well as a number of papers
and references. Due to the relatively large number of compounds
of interest to us, a full-scale pharmacological testing program
is not really feasible. However, we feel that sufficient
information can be derived from three specific tests. The first
is the effect of nicotine analogues on the isolated rectus-abdominus
muscle of the frog, a skeletal muscle with a cholinergic receptor
at the neuromuscular junction. Included is a report by Haglid
and Wellings which discusses this particular test (as well as the
Art. 1, 126 (1967).
(see B. C. S. Hollands and S. Vanov, Brit. J. Pharmacol., 25, 307
(1965); D. J. Fishlock and A. G. Parks, Brit. J. P armacol., 26, 79 h,i,
(1966)). Several other papers of interest are: Q
~
-1. A. S. N!anivadekar and B. B. Gaitonde, Arch. Int. G:
Phiarmacodyn., 159, 200 (1966). ~
2
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Arch
Int. Pharmacodyni
164
345 (1966) "
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3. K. K. F. Ng, Brit. J. Pharmacol., 28, 228 (1966). ~
4. D. R. Curtis and R. W. Ryall, Exp. Brain Res., 2, 49 (1966).
The second test involves contraction of the isolated guinea pig
ileum, a smooth muscle. W'e would be interssted in the effect of a
given analogue on both the longitudinal and~circular muscles. The
effect on the longitudinal muscle is most probably cholinergic
in nature. However, the effect on the circular muscles is more
likely caused by the release of catecholamines, possibly norepinephrine
, r,
Dr. W. F. Gannon
Page 2
January 31, 1974
In addition, Clark has reported the effect of nicotine and a series
of its analogues on guinea pig ileum (M. S. G. Clark, M. J. Rand and
S. Vanov, Arch. Int. Pharmacodyn., 156, 363 (1965).
Lastly, in order to have data on a more complex nicotinic effect,
the effect of nicotine analogues on the cat's blood pressure is also
a suggested test. References are:
1. F. F. Cowan and L. H. Greene, Fed. Proc., 24, Pt. 1, 364
(1965). -
2. N. N. Share and K. F. Melville, Arch. Int. Pharmacodyn.,
153, 267 (1965).
3. G. L. G9bber,Fed. Proc., 28, 419 (1969'), J. Pharmacol. Exp.
Ther., 166, 255 (1969)~.
Also see Curtis and Ryall.
Appended'is a list of compotznds now on hand which we are--
interested in testing. Please excuse any pharmacological
inaccuracies since we are only chemists.
/mro
cc: Dr. T. S. Osdene
