Guanfacine: A possible drug to improve memory in old age

As you get old, you start to forget things. True. Not that you couldn’t forget things when you’re younger and distracted; but as you get older, perhaps you’re more easily distracted. Why would that be? There are many lines of research into the loss of memory capacity as we age. One such line is conducted by Amy Arnsten and a team of researchers at Yale University (New Haven, Connecticut, USA). Their work concentrated on the so-called ‘short term memory’ capacity of the pre-frontal cortex, that region of the brain most associated with moment-to-moment (real time) higher level mental activity. Using a variety of animals at various ages (young, middle aged, and elderly), they tested for firing rates in the pre-frontal cortex while the animals underwent working memory tasks. The results, reported in the journal Nature [27 July 2011, paywalled, Neuronal basis of age-related working memory decline] showed that as the animals age, the rate of neuron firing declines – which implies a loss of memory capacity.

What appears to happen is that the prefrontal cortex accumulates too much of the signaling molecule known as cAMP. It opens too many ion channels (the primary means of generating neuronal firing), which weakens the neurons. The researchers went to the medical chemistry shelf to look for agents that either inhibit or block cAMP sensitive ion channels and came up with guanfacine, a relatively common drug (Tenex is its proprietary name) used to treat attention deficit disorder (ADHD), anxiety attacks and sometimes high blood pressure. After applying this drug to older animals, they found that significant neuronal firing rate capacity was restored; again implying better short-term memory.

What’s significant here is not just that this is another shot at extending the length and quality of life, but that it has a reasonable scientific background AND it is moving into clinical trials (stage one). That is the significant part. If guanfacine proves to have beneficial effect on the memory of the elderly and doesn’t show any dangerous side effects or long-term problems – add it to the growing armamentarium against old age. It’s on such advances that the claim of human beings living to (at least) 150 years is made.

There is a hint of spaghetti-hitting-wall technique in this. (You know, the old “throw spaghetti against the wall and see what sticks” method of determining experimental evidence.) Or perhaps a taste of the magic elixir from the fountain of youth. But then, the search for longer, better life is probably as old as our awareness of aging and death. Sometimes solutions are found long before we know precisely why they work.

Research Spectrum

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2 Comments

  1. Tammy RN
    Posted October 7, 2011 at 11:31 am | Permalink

    Low dose guanfacine BID is a great alternative to lisinopril. Lisinopril is linked to hearing loss, tinnitus, muscle cramps.

  2. Fonda
    Posted April 22, 2012 at 3:28 pm | Permalink

    Since I have started taking guanfacine, I have gained about 17 lbs, I have no energy. It has helped my B/P some. But it isn’t worth the weight and the fatigue.

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