Medications for childhood behavioral disorders: What are the effects?

Guanfacine is an old medication for hypertension, marketed as Tenex. It's thought to act by stimulating alpha2-adrenergic receptors in the brain; in other words it's an alpha2-adrenoceptor agonist.

It's not a great antihypertensive and it's not used much for blood pressure treatment any longer. It is used, off label, for the management of some behavioral disorders in children.

What effect, I wondered, might it have on the developing brain?

It wasn't hard to find this on Pubmed.

Activation of alpha2A adrenoceptors alters dendrit...[Brain Res. 2008] - PubMed Result

Activation of alpha2A adrenoceptors alters dendritic spine development and the expression of spinophilin in cultured cortical neurones.

Hu J, Vidovic M, Chen MM, Lu QY, Song ZM.

Division of Neuroscience, John Curtin School of Medical Research, and Medical School, Australian National University, Canberra, ACT, Australia; State key laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060 China.

alpha2 adrenoceptors have been shown to regulate the development of dendrites in mammalian cortical neurones. In this study we have investigated how agonists of alpha2 adrenoceptors affect length and density of dendritic spines in cultured cortical neurones from C57/B6 mice. A twenty-four hour incubation of 14 day old cultured neurones with UK 14304, an alpha2-adrenoceptor agonist, resulted in a significant increase in the average length and density of dendritic spines. Furthermore, incubation of neurones with the selective alpha2A agonist guanfacine resulted in 1.2-fold increase in spine length and 1.8-fold increase in spine density. These effects were blocked by RX 821002 and BRL 44408, alpha2- and alpha2A-adrenoceptor antagonists, respectively. The observed changes in the density and length of dendritic spines were correlated with increased expression of spinophilin, a key cytoskeletal protein in the formation and maintenance of dendritic spines, and a decrease in the phosphorylation of spinophilin on serine residues. The latter finding points to a possible mechanism by which adrenoceptors may regulate spinophilin function in dendritic spine development and structure in cortical neurones in vitro.

It seems likely then that Guanfacine alters the course of neuronal development in humans, as it does in mice.

So, is this a good thing, or a bad thing?

We don't know.

There's a lot here to think about, on several different levels.