Guanfacine

Also Known As: Guanfacine, Tenex, Intuniv

Guanfacine (brand name Tenex, and the extended release Intuniv) is a sympatholytic. It is a selective α2A receptor agonist. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal cortex. Guanfacine lowers both systolic and diastolic blood pressure by activating the central nervous system α-2a norepinephrine autoreceptors, which results in reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone. Its side-effects are dose dependent, with practically no dryness of the mouth at doses of 2 mg and less.

It reduces hypertension not just in short-term, but also as shown in long-term studies with normalization of blood pressure of 54% treated over a year and 66% over two years.[4]

An extended-release formulation of guanfacine (Intuniv) has also been approved by the FDA for the treatment of attention-deficit hyperactivity disorder (ADHD) in people ages 6-17. Its beneficial actions are likely due to its ability to strengthen prefrontal cortical regulation of attention and behavior.[5] Guanfacine is also used in conjunction with stimulants to augment therapeutic actions, counter side effects, reduce rebound, and when taken at night, to induce sleep.[6] Guanfacine is thought to improve regulation of behavior, attention, and emotion through actions at post-synaptic alpha-2A adrenergic receptors on prefrontal cortical neurons, which strengthen prefrontal cortical network connections.[7] In animal models, guanfacine is seen to affect a number of cognitive factors, including working memory improvement, distractibility reduction, response inhibition improvement, and attention control.[5] Performance increases in spatial working memory have also been observed in humans.[8] Another study found no effect on healthy male adult's executive functions and working memory, and small decrements on 2 tasks relating to the sedative effect of guanfacine.[9]

Another psychiatric use of guanfacine is for treatment of anxiety, such as generalized anxiety disorder and post-traumatic stress disorder symptoms. Guanfacine and other alpha-2A agonist reduce sympathetic arousal, weaken the emotional responses of the amygdala, and strengthen prefrontal cortical regulation of emotion, action and thought. All of these actions likely contribute to the relief of the hyperarousal, re-experiencing of memory, and impulsivity associated with PTSD.[10] Due to its prolonged half-life, it also has been seen to improve sleep interrupted by nightmares in PTSD patients.[11]


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