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Mr. Kreidler. Thank you, Mr. Chairman. You have said that the 

 purpose of the analogue program was to develop a nicotine ana- 

 logue that had the brain effects of nicotine, but not the heart ef- 

 fects, if I recall correctly. Was the initial idea, as far as you under- 

 stand, to develop a safer cigarette? 



Mr. DeNoble. That's correct, yes. 



Mr. Kreidler. Where were the analogues developed? 



Mr. DeNoble. They were synthesized at the Richmond center, 

 the organic laboratory. 



Mr. Kreidler. And do you know who headed that clinical group? 



Mr. DeNoble. Dr. Jeff Seaman headed the group. Chuck 

 Shevdarian was also another chemist in the group. 



Mr. Kreidler. They were at Philip Morris then? 



Mr. DeNoble. They were back in 1984. I don't know where they 

 are now. 



Mr. Kreidler. OK. It is my understanding that part of the ana- 

 logue testing was done in Rochester and part in Richmond. Could 

 you tell us what the relationship between the work in Rochester 

 and the work in Richmond was? 



Mr. DeNoble. Yes. The analogues would be synthesized in Rich- 

 mond, Va., and they would first be sent to Rochester, Dr. Leo 

 Abood's laboratory. What Leo would do would be screen the ana- 

 logues in a receptor binding assay, to see whether the analogue rec- 

 ognized the nicotinic receptor, you know, in brain. He was using 

 torpedo fish membranes, but it's the same thing. 



At that point we would determine whether or not it had the 

 same — whether the receptor said, gee, you look like nicotine. We 

 would then get some data on whether or not it produced contrac- 

 tions in guinea pig ilium, which would be a predictor of cardiac ac- 

 tivity. 



At that point, that data would be sent back down to us in our 

 laboratory, and we would screen the compound. If it was good data, 

 if it met the criteria of good data, we would screen the compound 

 in our tests in animal behavior to determine whether it looked like 

 nicotine. 



Mr. Kreidler. So it was, at least, the tobacco version of nicotine 

 that was causing the cardiovascular type of reaction then, as far 

 as you could determine? 



Mr. DeNoble. I'm not sure I understand the question. 



Mr. Kreidler. The cardiovascular responses of nicotine were as- 

 sociated with the tobacco form, and there were perhaps some other 

 forms of nicotine 



Mr. DeNoble. There is a couple of different forms of nicotine, 

 but the presser effect you get is with the L-form of nicotine, yes. 



Mr. Kreidler. I see. I would like to distribute Exhibit 18-A, 

 which was part of the 1980 memorandum explaining the work of 

 the nicotine receptor program in Rochester, Mr. Chairman, if that 

 is all right? 



Mr. Waxman. Without objection, that will be submitted for the 

 record, and identified as the next exhibit in sequential number. 



[Exhibit 18A follows:] 



