Samuel Gershon: The Tacrine paradigm


        I would like to bring up a pursuit of research area that needs to be looked at more closely. I will use an example that I had some association with over many years. This is the story of a compound abbreviated as THA (tetrahydro acridine - 1,2,3,4, tetrahydro-5-aminoacridine) and more well known as Tacrine. We worked on it first when I was in the Pharmacology Department at the University of in Melbourne in Australia.

        THA was synthesized by Professor Adrian Albert at the Australian National University in Canberra who gave us access to study it in the Departments of Pharmacology and Microbiology. Our studies in psychiatry were targeted to looking at its Central Nervous System (CNS) effects. It was found that it was a stimulant and analeptic. In both animals and man it produced clear antagonism to morphine or barbiturate induced sedation or coma.  It had generally alerting and stimulant effects after anesthesia. THA was approved as a treatment of imipramine overdose and someone took out a patent for this purpose.

        In the US several investigators tried it for the treatment of senile dementia and obtained a patent for this use. Subsequently, THA was approved by the FDA for the treatment of senile dementia. It was marketed in the US for this indication.  The question arose as to whether THA provided a rational treatment for senile dementia based on its pharmacological properties.

        Then the reported claim for effectiveness in the treatment for senile dementia was modified. Instead of being claimed that it was an effective treatment of senile dementia, it was claimed that it slowed the rate of deterioration. Very shortly thereafter its usage in senile dementia was dropped. Then THA was withdrawn from the market.

        I have two questions. What benefits did THA actually offer in the treatment of senile dementia? What were the findings that justified its approval for clinical use in senile dementia and its wide usage for this indication?

        There is a history of many compounds that have travelled a similar path. I think we may have some current compounds that may be travelling a similar path. Ketamine might be one of them, approved currently for the treatment of depression to be used for rapid onset via IV or a nasal spray.

        I think the “scientific research” behind these compounds is of concern.

March 5, 2020