- Marmor, R.S.
- Minnemeyer, H.J.
Design changes which have measurably altered health effects of cigarette smoke, both for smokers and nonsmokers.
Measuring overall toxicity
Development of scientifically valid protocols and methods for testing the health and toxicity effects of changes in product design.
Toxicity and consumer intake
Development of scientifically valid procedures for measuring biological activity and neurological effects of nicotine and smoke constituents.
Use of additives
Modification of tobacco products through use of additives and measuring effects on dependence, behavior, and toxicity.
Design Componentanti-ciliastatic agent
Subjectnicotine analogues (Technology)
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TO: Dr. H. J. Minnemeyer
FROM: R. S. Marmor
SUBJECT: PMO Analogs
History of Project
_ March 31, 1977
On September 8, 1975, I proposed in a memo to you
that we initiate a structure activity relationship study
on PMO by preparing a number of analogs of PMO and arrang-
ing to have a ciliastasis remission bioassay perforn,ad.
For a commitment of relatively few man-hours, this would
give us valuable information as to whether more potent
PMO analogs exist, on the molecular nature of the bio-
activity, and a better stance in patent protection.
Over the next few months, 21 analogs were prepared.
Most were observed to have less intense and more Aleas2nt
odors than PMO. ~
In a memo on April 13, 1976, I listed the 21 compounds
we prepared and informed you that Dr. Tong had an
interest in evaluating PMO and analogs for ciliastasis
remission activity by an approach different than that
employed by Prof. Dalhamn. On talking further with Dr.
Tong, he stated that once the system was built and operable,
the testing of the analogs could be quickly performed.
Dr. Schultz requested at that time that when data was
available supporting activity of the analogs, we should
consider expanding the scope of existing patents. On
July 2, 1976, my memo to Dr. Tong stated we were ready
to supply him with any samples whenever he could begin.
Memos from Dr. Tong to you on October 1, 1976 and from
Mr. Heck to you on November 2, 1976, indicated that the
apparatus would soon be ready to begin bioassay. On
March 14, 1977 in Lorillard Report #973, Dr. Tong reported
on the absence of mutagenicity and high dose toxicity C
for 20 of the PMO analogs. ~
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Dr. H. J. Minr.emeyer - 2 - March 31, 1977
Control data for the chicken trachea ciliastasis
remission experiment is presently being gathered.
When this phase is complete, PMO will be studied, then
testing will begin on the analogs. Further work on any
active analogs would be anticipated.
It is my opinion, drawn from the history of this
project and the present priority level this project is
being given, that there is little chance of having
completed analog data in hand by the end of this year.
Proposed Further Work
It is premature to discuss further experiments at
this time. The question now is, are there analogs of
greater activity than PMO? If there are, we expect
that they can be employed on cigarettes at lower dose
levels such that the flavor and delivery problems will
disappear. Will these more desirable analogs be
without undesirable physiological effects such as
bronchiodilation? Are we to ignore research on these
analogs because additional biological testing would
be costly and time-consuming? The trend in cigarettes
to low tar-high filtration design further increases
the need to investigate PMO analogs.
R. . Marmor
Xc: Dr. F. J. Schultz