Because the PFC is required for working memory and attention, it is thought that clonidines inhibition of PFC neurons helps to eliminate irrelevant attention (and subsequent behaviors), improving the persons focus and correcting deficits in attention. Growth hormone test
Clonidine stimulates release of HGH hormone from the hypothalamus, which in turn stimulates pituitary release of growth hormone. This effect has been used as part of a "growth hormone test," which can assist with diagnosing growth hormone deficiency in children. Pharmacokinetics
After being ingested, clonidine is absorbed into the blood stream rapidly and nearly completely, with peak concentrations in human plasma occurring within 60–90 minutes for the "Immediate Release" (IR) version of the drug, which is shorter than the "Extended Release" (ER/XR) version. Clonidine is fairly lipid soluble with the logarithm of its partition coefficient (log P) equal to 1.6; to compare, the optimal log P to allow a drug that is active in the human central nervous system to penetrate the blood brain barrier is 2.0. Less than half of the absorbed portion of an orally administered dose will be metabolized by the liver into inactive metabolites, with roughly the other half being excreted unchanged by the kidneys. About one-fifth of an oral dose will not be absorbed, and is thus excreted in the feces. The half-life of clonidine varies widely, with estimates between 6 and 23 hours, and is greatly affected by and prolonged in the setting of poor kidney function. History
Clonidine was introduced in 1966.
When given intravenously, clonidine can temporarily increase blood pressure by stimulating α1 receptors in smooth muscles in blood vessels. This hypertensive effect is not usual when clonidine is given by mouth or by the transdermal route. : 201–203 Plasma concentration of clonidine exceeding 2.0 ng/mL does not provide further blood pressure reduction. Attention deficit hyperactivity disorder
In the setting of attention deficit hyperactivity disorder (ADHD), clonidines molecular mechanism of action occurs due to its agonism at the alpha-2A adrenergic receptor, the subtype of the adrenergic receptor that is most principally found in the brain. Within the brain, the alpha-2A adrenergic receptors are found within the prefrontal cortex (PFC), among other areas. The alpha-2A adrenergic receptors are found on the presynaptic cleft of a given neuron, and, when activated by an agonist, the effect on downstream neurons is inhibitory. The inhibition is accomplished by preventing the secretion of the neurotransmitter norepinephrine. Thus, clonidines agonism on alpha-2A adrenergic receptors in the PFC inhibits the action of downstream neurons by preventing the secretion of norepinephrine.This mechanism is similar to the brains physiological inhibition of PFC neurons by the locus ceruleus (LC), which secretes norepinephrine into the PFC. Although norepinephrine can also bind to target adrenergic receptors on the downstream neuron (otherwise inducing a stimulatory effect), norepinephrine also binds to alpha-2A adrenergic receptors (akin to clonidines mechanism of action), inhibiting the release of norepinephrine by that neuron and inducing an inhibitory effect.