http://exhibits.library.stonybrook.edu/mfp/files/original/2c170ecde2c5784e8f07a062c10eb68d.pdf 5609f5c2406d7b6449fb5af08c8f4105 PDF Text Text Reprinted from: E. ROTHLIN (Editor), Neuro-Psychopharmacology, Vol. 2 (1961), Proceedings of the 2nd International Meeting of the Collegium Internationale Neuro-Psychopharmacologicum, Basle 1960 From the Discussion to the First Symposium: THE PROBLEM OF ANTAGONISTS TO PSYCHOTROPIC DRUGS MAX FINK Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, N. Y. (U.S.A.) ’ It has been a privilege and a pleasure to read and to listen to the reports by Drs. and DENBER. These authors have approached the problem of antagonists to psychotropic drugs from different vantage points: Dr. GADDUM that of the pharma— cologist — theoretician, assessing general issues; and Dr. DENBER, the experimental clinician with a specific problem exemplifying a theoretic principle. Dr. GADDUM essayed a broad classification of drug antagonisms emphasizing c0mpetitive inhibition. While studies of this concept have a likelihood of clarifying our GADDUM References p. 32. �DISCUSSION 31 knowledge of drug action, there was little that could be specified at present. This View, founded on extensive experience, suggests that a critical appraisal is necessary of the and of relation theories serotonin, fanciful the 5—hydroxytryptophan recent on many amine oxidases, amongst others, to human psychoses. If I interpret Dr. GADDUM’s review correctly, he is describing basic postulates which must be satisfied before drug antagonisms are established, and such establishment is requisite to the determination of the site of action of such interactions. Dr. GADDUM notes, that for the determination of competitive inhibition, four considerations must be fulfilled, i.e.: I. control drugs are not inhibited; 2. antagonistic actions are demonstrable at several sites or systems; 3. dose relationships are systematic; and 4. agents have a common chemical grouping. To these I would also add, that for such determinations of competitive inhibition to have significance for human psycho—pharmacology, the antagonisms should not be based on work limited to a single animal species, but should be demonstrated in man. Dr. DENBER has approached the problem from a specific experiment — the meas— urement of changes in various blood chemical elements and gross clinical behavior in chronic relapsing psychotic subjects. These patients were studied before and after intravenous mescaline followed by a variety of phenothiazine agents administered as “antagonists”. Dr. DENBER confirmed his earlier studies that various phenothiazine derivatives, excepting diethazine, are effective in modifying mescaline clinical affects; and that such effects are related to the halogenation of the chemical ring structure. Parenthetically, we can confirm the observation that diethazine is not an antagonist for hallucinogens, for in our studies diethazine induced illusory states and EEG desynchronization in psychiatric patients, similar to mescalinel. The biochemical data indicates the wide range of behaviors altered by these broad acting agents. Like his earlier studies on the changes in the EEG, and the observations from others of the blocking of induced psychotomimetic effects as measured in frame— theoretic from be this data must a analyzed etc., mood, perception, language, work of the relevance, or imputed causal relations, of such observations to clinical behavior. No such framework is given and the assumed connection between these blood changes and clinical behavior is obscure. Indeed, Dr. DENBER concludes that: “In all probability, the reactions observed represent part of a total body response to a stress-. . Assuming this conclusion is a reasonable working hypothesis, we are taxed by the problem of critical experiments to elucidate the body response to psychotomimetic and psychotropic agents. In this task we are faced by a number of monumental problems, and it is here that Dr. GADDUM’S principles and Dr. DENBER’S experiments approach a common base, albeit tenuous. For what Dr. GADDUM fails to indicate in his principles are the significant behaviors to be studied; while Dr. DENBER selects be— interactive clinical of and —~that blood of behavior global chemistry two aspects havior — as dependent variables. It is the selection of significant experimental variables and their quantification that represents a central problem of human psychopharmacologic research today. Assuming that the laws of human interpersonal behavior are the goals of our studies, and that psychopharmacology represents one aspect of the modification of human References 12. 32. �FIRST SYMPOSIUM 32 interpersonal behavior, what evidence is there that any single aspect of task behavior is correlated with changes in interpersonal behavior induced by drugs? I am troubled by the fact that innumerable investigations have selected a single or few variables on the biochemical level and correlated these with a single or few variables on the behavioral level, the selection of which is not designed to elucidate a theoretic framework but rather based on a vague personal notion. Thus, investigator after investigator selects pole climbing, bar pressing, conditioned avoidance, jiggle cage movement, etc. as single variables in a wide range of animal studies; and rating scales, self—ratings, psychomotor tasks, EEG, blood pressure, and many others in human studies as single significant variables. Few studies assess the relevance of these tasks for the prediction of the direction or efficacy of drug effects on interpersonal behavior. Other significant problems include that of generalizing from non—psychopathic populations to our understanding of disordered human behavior. A sub—aspect of this problem is the generalization from one psychopathic population to another without fully taking into account such population factors as genetic predisposition, early organic traumata, varying acculturation processess and sociologic status upon population characteristics. These aspects may so alter the observations obtained with a specific pharmacologic agent as to give varying, and occasionally opposite results when similar studies are done in different settings. Some years ago, Dr. ABRAHAM WIKLER outlined the problem facing experimental psychopharmacologistsZ. In assessing the relation of psychopharmacology to experimental psychiatry, he recommended: “In psychiatry we need more properly controlled studies on the comparative effects of a variety of drugs, on the behavior of varied, but selected, homogeneous groups of subjects, under varied but standardized experimental conditions, and with varied but specified activities of the observer.” In this I concur and commend it to the Collegium as the most logical beginning to the resolution of the problems of antagonists to psychotropic agents. REFERENCES 1 2 M. FINK, Effect of anticholinergic agent, Diethazine on EEG and behavior: significance for theory of convulsive therapy. A .M.A. Arch. Neurol. Psychiat, 80 (1958) 380. A. WIKLER, The Relation of Psychiatry to Pharmacology, Williams & Wilkins, Baltimore, Md., I957- Printed in‘ The Netherlands �‘ w33;; érn‘msmfi‘ ’1angmgemam: $§i~wgfl .91»: ~' ‘iWMem 423d mmhm: maximmmvmfi .: {Err thwxsfisw 9mm: fim téfim, , . . 1 . Mamiew. > �D First I I S C U 3 8 Synponiun TH! PROBLBH'OF ANTAGOHISTS lax 713k, ~ 0 l 0.1.H.P. TO PSYCKOTROPIC DRUGS H.D. Pro. tho Depart-ant o! Bxporinontal Psychintry, Billlido Hoapitnl, clan Oaks l.!. July hth, 1960, 3:310, Switaorland �It listen has been a privilege and a pleasure to read and to to the reports by Drs. Gaddun and Denber. These authors have approached the problem or antagonists to psychotropic drugs from different vantage points Dr. Gaddna that or the pharmacologist - theoretician, assess~ ing general issues; and Dr. Denber, the experimental-clinician with a specific problen exeaplitying a theoretic principle. — Dr. Gaddnn essayed a breed classification of drug antagonisns emphasising conpetitive inhibition. While studies of this concept have a likelihood of clarifying our knowledge of drug action, there was little that could be specified at present. This view, founded on extensive experience, suggests that a critical appraisal is necessary d’the nany recent fanciful theories on the relation of serotonin, S—hydroxytryptephan and anine oxidases, alongst others, to huaan psychoses. It I interpret Dr. Gaddun's review correctly, he is describing basic postulates which must be satisfied before drug antagonisns are established, and such establishnent is requisite to the deternination of the site of action or such interactions. Dr. Oaddna notes, that for the determination of competitive inhibition, four considerations nuet be fulfilled: i.e.: (1) control drugs are not inhibited; (2) antagonistic actions sre demonstrable at several sites or systems; �To (3) dose rslaticnships are systoaaticg and (h) agonts hsvs a con-on cboaical grouping. that would for ouch dotorsinatioos of thoss I also add, coapotitivo inhibition to have significance for huaan psycho~ pharmacology, tho antagodsus should not be basod on work bo doaonstrablo should but aniacl a to spacios, single liaitod in san. Dr. Donbor has approacbad tho probloa Iron a spocitic oxpariaont - tho aoasursaont of changoa in various blood ohsaical closonta and gross clinical behavior in chronic rolapsiog psychotic and intravonous botoro Thoso studiod attor scro patioots subjects. aoscalino followed by a varicty of phonothiasino agonts adaioistorod so *antsgonists'. Dr. Donbor contirsod his oarlior studios that various phonothiosino dorivativos, oxcspting diothasino, aro ottoctivo in soditying aoscalins clinical atrocts; and that such ottocts arc rolatod to tho halogonation of tho choaical ring structuro. Paronthotically, so can contira tho cbsorvation that diothasino is not an antagonist for hallucinogons, for in our studios diotbasino iodacod illusory stats: and EEG dosynchronisatioc in psychiatric potiouts, aioilar to aoscalino (1). Tbs biochoaicsl data indicatos tho aids songs of bohaviors altorod by thoso broad acting scouts. Liko his oarlior studios? on tho changos in tho EEG, and tho cbsorvations from othors of tho blocking of indccod psychctoaiaotic ottocts as Ioascrod in bo snot data analysod this languago, aood, porcopticc, otc., �-3Iron a theoretic fraaevork of the relevance, or iapcted cancel relatione, of anch obeervationa to clinical behaviour. No Inch fraaevork ia given and the aeauaed connection between these blood changee and clinical behavior in ebecnre. Indeed, Dr. Denber that: "In all probability, the reactione obaerved repreeent part or a total body reaponee to a atreaa- ...' leenaing thie conclnaion ie a reaeonable working hypo-» theeie, we are taxed by the problea of critical experiaente concludee to elucidate the body reeponee to peyohotoaiaetic and paychetropic agent. In thia teak we are faced by a nnaber of aonnaental probleae, and it ie here that Dr. Gaddna'e principlee and Dr. Denber’a experiaenta approach a coaeon baae, albeit tennoce. For what Dr. Gaddna taile to indicate in hie principlee are the eignificant behaviore to be atodied; while Dr. Denber eelecte two aapecta of behavior - that of blood cheaietry and global clinical interactive behavior - aa dependent variables. It in the eelection or significant experiaental variablee and their quantification that repreeente a central problea o: hnaan peyohopharaacologic reeearch today. ieanaing that the lava o: hnaan interpereonal behavior are the goale or our etndiee, and that paychopharnacology repreeenta one aepect of the aodification or hnaan interperaonal behavior, what evidence ie there that any single aepect of teak behavior is correlated with ehangee in interpereonal behavior induced by drugs? �-1... I on troubled by the tent thet innnnereble investicetione heve eelected e eingle or ten veriehlee on the bieeheeioel level end correleted theee with e eincle or ten verieblee on the behevierel level, the eelectien or which ie not deeigncd to elncidete e theoretic freeeeork but rether beeed on e vogue pereenel notion. Thne, inveetigetor efter inveetigetor eelecte pole cliebing, her preeeing, conditioned evoidence, Jigcle cege leveeent, etc. ee eingle veriehlee in e wide reuse of enieel etndiee; end retina ecelec, eelt-retinge, peyohoeotor teeke, EEO, blood preeenre, end eeny othere in hneen etndiee ee single eixnificent verieblee. rev etndiee eeeeee the relevence of these teeke tor the prediction of the direction or etficecy o8 drug ettecte on interpereonel behevior. Other eigniticent prohleee include thet o: generelieing tree non-peyohopethio populetione to our underetending of dieordered hneen behevior. e eobaeepect of this problee is the generelieetien free one peychopethic populetion to enother without ench eccount into populetion rectore ee genetic teking telly prediepoeition, eerly orgenic tredeete, verying eccnlturetion proceeeee end eociologio etetne upon popnletion cherecterietice.» Theee eepeote eey eo elter the oheervetione chteined with e epecifio phereeoologic egeet ee to give verying, end oceeeionelly opposite reenlte when eieiler etndiee ere done in different settings. �-5Solo yoara ago, Dr. Ahrahaa Hiklor ootlinod tho prohloa In aoooooiog (2). paychopharacologiato oxporiaontal facing tho relation of poyohopharoacology to oxporioontal psychiatry, ho roconaondods 'Iu poychiatry Io nood noro properly controllod otndioo on tho oooparativo ottocto of a variety of drogo, on tho behavior of variod, hot ooloctod, hologonoooo groups or ouhaooto, undor variod hot otandardiaod oxporiaontal conditiono, and with variod but opocitiod activitioa of tho oboorvor.’ In this I concur, and connond it to tho collogiuo an the aoot logical hoaiuning to tho roaolution of tho prohloao of antagoniota to psychotropic agonto. �1. link, n: Effect at Antieholinergic Agent, Dietheeine3on EEG end Behavior: Significance fer Theory of Convaleive Therapy. .§_o_ 2. "‘ AHA Arch. figural. a Pezehiet. 380‘387, 1958. Hitler, A: The Relation of Pezphiatrz to Phernecologzl In. Wilkins, Beltinere, 1957. � 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 Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. 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 Problems of antagonists to psychotropic drugs, 30-2 (Discussion, Neuropsychologic response patterns of some psychotropic drugs). Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-51-017 Date A point or period of time associated with an event in the lifecycle of the resource 1961 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 Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprint and [preprint]. Reprint from: E.ROTHLIN (Editor), Neuro-Psychopharmacology, Vol. 2 (1961), Proceedings of the 2nd International Meeting of the Collegium Internationale Neuro-Psychopharmacologicum, Basle 1960 From the Discussion to the First Symposium: THE PROBLEM OF ANTAGONISTS TO PSYCHOTROPIC DRUGS 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. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published