Created: 1/22/1960

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Project-Title: The Synthesis end Biochemical Evaluation of Potential Psychopharmaco-loglcal Agents.

Principal Investigator: Professor and Head of the Department

orTriarSceutic^rand Medicinal Chemistry, College of.

For tho past several years, the applicant has been engaged in research involving (I) the synthesis of organic entitles having potential effects upon the centralsystem, and (II) the evaluation of connections between the chemical andproperties of these compounds. The applicant is primarily interested la the fundamental study of relationships between molecular constitution andresponse, and Is particularly concerned, with the effect of gradual changes In the chemical structure of synthetic entitles upon Isolated enzyme systems. TheIs referred to (A) reports submitted earlier to the Geschlckter Fund for Medical Research,, and (B) published9 foc supplemental information.

The applicant plans to continue his Investigation In accordance with the principles set forth in tha cited cceamraicatloos. Specifically, he Intends to:

Synthesize several series of new compounds patterned after (a) organicnown to affect the central nervous system, and (b) moieties acknowledged asIn enzyme systems implicated In the pharmacodynamics of compoundspsychopharmacological properties. The member compounds of each series will be designed with gradual changes In their constitution, or physical properties, or both; furthermore, they will be planned Inanner that potentialIn the Interaction between the member compoundsiven synthetic seriesiven enzyme may be interpreted In terms of concepts reasonably wellin contemporary theoretical chemistry.

Study the effect of these entitles upon (a) Isolated enzyme preparations believed to ba associated .with brain function, and (b) other plausible biochemical systems.

Explore relationships'between the biochemical activity "of. each series ofthe successive changes in the chemical and physical characteristics of


At present, our synthetic work la centered around series of arylalkylamlnoalkylaceta-mldcs, and pyridine- and piperIdInecarboxamldes which could be visualized as moieties derived from the psychotomimetic molecule LSD (see Figures I, II, HI and TV;eries have been planned).

* Effective July 1,0 (on leave of absence July 1,0 through



Concurrently, the completed compounds are being evaluated In Isolated chollnesterase systems In which LSD has shown remarkable specificity. Our maoometric procedures

Page Six

yield very precise measurements of activity in isolated pseudo- .andsystems, end enable us to evaluate tha significance of even minor variations In activity due to small constitutional changeseries of molecules.

We are aware of the fact that tbe effectivenesssychopharmacologlcal agent in vitro cannot be interpreted as evidence for the involvement of the specific enzyme in the mechanism of psychotomimetic responses, ret even without conclusive causal connection, this'approach may furnish valuable information on the nature of psycho-pharmacological agents.



It is felt that this investigation may yield (a) information assisting theof interrelationships between molecular constitution and biological response, (b) better insight into the biochemical characteristics and therapeuticof certain types of etoletles, (c) several series of new organic compounds and Information about their physical characteristics, and (d) data supplementing our knowledge of the naurochemicsl processes associated with the action ofagents.


The references cited In the first paragraph of the outline are listed on thepage.

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apprttufd for rf1ease date:2

Original document.

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