Central effects of guanfacine and clonidine during wakefulness and sleep in healthy subjects.

Abstract

1 Three double-blind studies in young normotensive male volunteers were carried out: a study in ten awake subjects, comparing guanfacine 2.0 and 4.0 mg with clonidine 0.15 and 0.30 mg and placebo; and two polygraphic sleep studies each with six subjects, comparing guanfacine 1.0 and 2.0 mg with-placebo, and clonidine 0.15 and 0.30 mg with placebo, respectively. 2 In awake subjects, both drugs reduced systolic blood pressure without significantly altering diastolic blood pressure, pulse rate and objective performance parameters. 'Side-effects' such as tiredness, decreased inclination to work, and dryness of the mouth were somewhat more frequent after the higher clonidine dose than after both doses of guanfacine, and peaked 2 h after clonidine but only 4-6 h after guanfacine. 3 Clonidine 0.15 and 0.30 mg given in the evening was followed by a substantial and dosedependent reduction in rapid eye movement (REM) sleep. Guanfacine 1.0 mg did not alter REM sleep and 2.0 mg of guanfacine had less effect than both doses of clonidine in this respect. Clonidine's effect on REM sleep began after about 2 h, whereas guanfacine's action on REM sleep began 5 h after the dose. 4 Guanfacine and clonidine possess a qualitatively similar pattern of activity with regard to the parameters studied; but the central effects are less pronounced and occur later after guanfacine than after clonidine in equiactive doses.

Attention-deficit/hyperactivity disorder and adverse health outcomes

“…Even so, medications can complicate the clinical picture, since psychostimulants can increase sleep-onset latency (Weiss & Salpekar, 2010). Conversely, α 2 -adrenoceptor agonists have been used to facilitate sleep, although there are limited data regarding their impact on sleep parameters (Spiegel & DeVos, 1980; Weiss & Salpekar, 2010), and even afternoon doses of traditional stimulants may sometimes improve sleep in children with ADHD (see discussion in Spruyt & Gozal, 2011). …”

Assessment of safety, cardiovascular and subjective effects after intravenous cocaine and lofexidine

“…That lofexidine targets imidazoline receptors and decreases presynaptic noradrenergic release and subsequent sympathetic drive may account for the prominence of this AE in the present study. A more specific α-2 adrenergic receptor agonist, such as guanfacine, may be worth evaluating since it is less sedating, better tolerated, has a longer half-life, and has more selectivity for α-2 adrenergic receptors found in prefrontal cortex (Nami et al 1983; Ramos et al 2006; Spiegel & DeVos 1980). Of particular interest, a recent study in 20 cocaine-dependent individuals showed that guanfacine lowered stress- and cue-induced nicotine craving and cue-induced cocaine craving, anxiety and arousal (Fox et al 2012); suggesting that guanfacine warrants further study.…”

Electroencephalographic and Psychometric Assessment of the CNS Effects of Single Doses of Guanfacine Hydrochloride (Estulic®) and Clonidine (Catapres®)

“…CNS-depressant effect. This also suggests the possibility of an effect on waking and sleeping cycle [33]. According to a classification of the typical waking EEG profiles of psychotropic drugs in healthy volun teers [10], they would be classified as sedative drugs.…”