http://exhibits.library.stonybrook.edu/mfp/files/original/965ac56cb625a1364d394f00e7f4693a.pdf 366544eacb662052e3aad6ee3546ad7d PDF Text Text November 20, 197h E. N. Terry, M. D. Medical Director Pharme Research (Canada) Ltd. 250 Hymns Boulevard Points Claire, P.Q., Canada Dear Stitch, I was pleased to review the data for the compound Si 93. The volume consisted of three parts: pharmacology and toxicology, dated 19 August 1970; clinical pilot studies dated November 2, 1972; and psychometric studies dated June 17. l97h. :m— wmw-ww The pharmacologic evidence indicates that Si 93 is atropine— like with tachycardia, mydrinsis, and dry mouth as predominant symytons. It is readily absorbed and at high doses inhibits gastric secretion. The anticholinergic actibity was also manifest in EEG studies-in rabbits and cats where 81 93 exhibited atropine-like patterns. The anticholinergic activity suggested its use as a spasmolytic. In the clinical studies, the dose range is defined. At there were no effects. At ho mg. anticholinergic and sedation occurred. At 60 mg, the subjects complained of fatigue and drowsi5 mg, . < ness in addition to the anticholinergic effects. In a crossover controlled study of 25 ng and 50 mg Si 93, the differences between the two doses were small with greater changes in pulse rate for the 25 mg dose. «luv-v nun-m nu-~4-uexlrw-mu—wxrfl g m... .m—v v“ mwn.mrv'flil‘flrr”" ,‘I'VIVFIE —'vr‘4 —v test data reportfl’interesting findings. Eight volunteers were seen in a double-blind crossoveg;gtndy of SI 93 Ild25 mg and 50 mg, oxasepen 20 mgI'IE’E'EOnparison substance, and placebo. The 50 mg dose of Si 93 elicited greater sedation than 20 mg oxasepan. but also an inner "stimulation". irritability, unpleasantness. feelings of warmth, and some clouding of sensorium. The 25 mg dose of Si 93 vss found to be pleasant and equivalent to The psychometric oxssepan. �,valnlrm...“ VW'K‘:"F ., ) ; ___.- er. , . y'vsc. .Y.. _new-m.,.. a._ “wees—w'cv a .>.. W2...”, .Infiu-VHW .“m-v. V V mm “4’".'—' v — - ~ V-- ~ '3 1- . sn-Mr-w rv-mww » 4-,“ w -m n. — » e. LF—IGY‘ ,, wan-VB;w-:’atv4‘lr:'t¢:gr:aw{v-a . ‘ / 4 E. N. Terry, 14.1). -2- November 20, 197k These observations strongly suggest that 81 93 has central at activity the doses studied; that the activity is pleasant and 'tranuillisina' at low doses, but unpleasant at high; that there a relatively narrow therapeutic range, for the 50 mg dose elicits is 'some of the central deliriant effects of the anticholinergics. There are interesting questions about the compound: Are the central effects similar to oxasepam (and other benzodiacepines). or like imipramine (ditran, and other thymoleptics)? some ‘Does 86 93 have a at lower doses, diphasic effect—~sedative and pleasant deliriant at higher doses? and stimulant and These questions can be answered by our present methods or electrophysiologic assay, for a classification study will define the Atype of central activity in man and yield evidence of its therapeutic range; and a dose-ranging study will give data for the stability or the nature of the central effects. ' However, the questions that must be answered by management before these studies are undertaken seem to me to be: Is there a need for a novel thymoleptic; and it there is, can 81 93 quality for further study since it may have a narrow therapeutic range? If the answer is affirmative and further studies are desired, to examine this compound. For a dose—finding study, single doses of 5.10.20, he and 60 mg should be examined. FOr a classi~ fication study, two doses and placebo could be examined in 10-12 sub-~ Jects over a post-drug four hour period with measurement of EEG, alert. ness, heart rate, blood pressure, mood ratings, symptom ratings, and critical flicker fusion (CFF). and the observations compared with our historical standard? diasepam and imipramine. we would be pleased my thanks {hr the opportunity to review these data in It seems to be an interesting centrally active originals.{ My compound. their German . best regards. Sincerely yours, Fink, M. D. Professor of Psychiatry Max Merd Again. “ah- .7 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Correspondence Text A resource consisting primarily of words for reading. 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Title A name given to the resource Correspondence to: Zimmerman, Kimblerly Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-05-00-027-8-574 Date A point or period of time associated with an event in the lifecycle of the resource 1974 Creator An entity primarily responsible for making the resource <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Correspondence -- Correspondence Relation A related resource The Max Fink Collection Description An account of the resource Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. 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