David Janowsky:Cholinergic muscarinic mechanisms in depression and mania 


An interaction between Max Fink and David Janowsky via Edward Shorter



Max Fink’s comment (January 3, 2020)


       Well, acetylcholine (ACh) again. I remember the excitement in the 1950s when EEG slowing conjured by induced seizures became associated with increased ACh in cerebrospinal fluid (CSF). Then, Denber found that diethazine inhibited slow waves and the patients who were responding to seizures with relief of depression, became anxious, crying, depressed again. I verified his report and went on to study CSF using clam hearts contraction as the index. My chemistry was poor, however, so I could not find increased ACh after seizures. Nevertheless, the animal data encouraged me to write my cholinergic theory of ECT in depression first in 1958 and then again in 1966 (Fink 1958,1966; Itil and Fink 1966). A forgotten road not travelled.

       The excitement associated with epinephrine by Kety and Schildkraut and the difficult chemistry of ACh led to the overwhelming enthusiasm for catecholamines, then selective serotonin re-uptake inhibitors (SSRIs), etc., etc.

       Fashions and hemlines are strong factors in psychiatry. Bring ACh back.




Bradley P, Fink M, editors. Anticholinergic Drugs and Brain Functions in Animals and Man. Progress in Brain Research, Vol. 28, Elsevier, Amsterdam, 1965; pp. 375. Fink M. Effect of anticholinergic agent, Diethazine, on EEG and behavior: significance for theory of convulsive therapy. Arch. Neurol. Psychiat. (Chic.), 1958; 80: 380-7.

Fink M. Effect of anticholinergic compounds on post-convulsive electroencephalogram and behavior of psychiatric patients. Electroenceph. Clin. Neurophysiol., 1960; 12: 359-69.

Fink M. Cholinergic aspects of convulsive therapy. J. Nerv. Ment. Dis., 1966; 142: 475-84.

Itil T, Fink M. Anticholinergic drug induced delirium experimental modification, quantitative

EEG and behavioral correlations. J. Nerv. Ment. Dis., 1966; 143: 492-507

David Janowsky’s reply (January 4, 2020)

Thanks so much for the comments... very interesting. Max, if you have a copy of the papers you quote, could you send them to me, or at least the references. I hope all is well with both of you. How true about fashions and hemlines. Are the hemlines up or down lately? I think the interest in ACh continues to hang on by a thread.


May 28, 202