Mechanism of action Receptor Ki (nM) Alpha-1A adrenergic receptor 316.23 Alpha-1B adrenergic receptor 316.23 Alpha-1D adrenergic receptor 125.89 Alpha-2A adrenergic receptor 42.92 Alpha-2B adrenergic receptor 106.31 Alpha-2C adrenergic receptor 233.1 The Ki refers to a drug's affinity for a receptor. The smaller the Ki, the higher the affinity for that receptor.<unk>  crosses the blood-brain barrier. High blood pressure<unk>  treats high blood pressure by stimulating α2 receptors in the brainstem, which decreases peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic α2 receptors in the vasomotor center in the brainstem. This binding has a sympatholytic effect, suppresses release of norepinephrine, ATP, renin, and neuropeptide Y which if released would increase vascular resistance.<unk>  also acts as an agonist at imidazoline-1 (I1) receptors in the brain, and it is hypothesized that this effect may contribute to reducing blood pressure by reducing signaling in the sympathetic nervous system; this effect acts upstream of the central α2 agonist effect of<unk> .<unk>  may also cause bradycardia, theoretically by increasing signaling through the vagus nerve. When given intravenously,<unk>  can temporarily increase blood pressure by stimulating α1 receptors in smooth muscles in blood vessels. This hypertensive effect is not usual when<unk>  is given by mouth or by the transdermal route. Plasma concentration of<unk>  exceeding 2.0 ng/mL does not provide further blood pressure reduction. Attention deficit hyperactivity disorder Structural comparison between the neurotransmitter norepinephrine and the drug<unk> . Both drugs bind to alpha-2 adrenergic receptors. Similarities between the two structures are shown highlighted in red. In the setting of attention deficit hyperactivity disorder (ADHD),<unk> 's 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<unk> eft 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,<unk> 's 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 brain's 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<unk> 's mechanism of action), inhibiting the release of norepinephrine by that neuron and inducing an inhibitory effect. Because the PFC is required for working memory and attention, it is thought that<unk> 's inhibition of PFC neurons helps to eliminate irrelevant attention (and subsequent behaviors), improving the person's focus and correcting deficits in attention. Growth hormone test<unk>  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,<unk>  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.<unk>  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<unk>  varies widely, with estimates between 6 and 23 hours, and is greatly affected by and prolonged in the setting of poor kidney function.
Clonidine
Brimonidine
Phenylephrine
Metergoline
Acebutolol
Prazosin
Drospirenone
Avacopan