Tobacco Documents Online

~. March 16, 1983 T. S. Osdene, Ph.D. Director of Research Philip Morris Research Center P.O. Box 26583 Richmond, Virginia 23261 Dear Tom: Enclosed is a report on the psychopharmacologic effects of the N'- substituted nicotine analogues. The drugs definitely appear to be tranquilizers, producing mild sedation and muscle relaxation (in rats). Although they are not as potent as the benzodiazepines (e.g. valium) they could conceivably have anti-anxiety effects. Furthermore, they are not depressants and might be of value in anxiety-related depression. For comparative purposes data are presented for valium. The preliminary tests involving only the assessment of overt behavior following IP and intraventricular adminsitration. When more material is available we can determine its anti-reserpine effect, prolongation in barbit- urate sleeping time, interacting with catecholaminergic systems, etc. You may wan,t to consider applying for patent for this class of compounds, since they are chemically unique and may possess some novel psychotherapeutic effects. Perhaps we can discuss this matter further at my next visit April 12, 13, 1983. Enclosed are abstracts of a ACNP meeting that may be of interest to you. Sincerely, ~;F" Leo G. Abood LGA:ca ~.~ ~ W.

- CR # Structure Dose (IP) mg/kg Sedation Body Tone Tranquilization (IVC) 50 pg ~o~~ ~ ~ ~,CK3 5 + + 2226 ~ 10 ++ + ++f~: 20 +++ ++ C 10 + + 2229 N'~ ~N 20 ++ ++ ~~ '~- ~-~ 10 + + - 2233 ~,1 o ~CHj 20 + + 7ZT ~ ~---- , 10 . 0 0 2228 fC , `t4 20 + 0 4+.+ ~l 10 0 0 2213 ~n ~ hl~{, 20 + 0 ~ ~ ~ 10 + 0 2250 ~~',~~. ~ ~. ~ 20 • ++ ++ ~ , 10 - 0 0 20 ++ + 4+ 1g _l 0 0 + 2282 - C0 ~ ~o ' N ~f~~ 2 + + Tranquilizing effects of various CR compounds in ra $ after intraperitoneal and intraventricular administration. ~000127514 "Sedation" was determined by measuring locomotion in an open field maze and the response to noxious (air blast) stimuli. "Body time" was estimated by handling rats and ability to hang from a rotor-bar. "Tranquilization" after IVC injection was estimated from muscle weakness in all four limbs, body tone, an& general activity. Rating scale was 0 - l+H. For comparative purposes, a dose of 5 mg/kg valium (IP) will have ++F+ in sedation and body tone, while 10 wg IVC will have a f+F+ in tranquilization. The duration of action of the CR drugs was 10-20 minutes IVC and about 30 minutes after IP injecti'on.