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.
Cold sensitivity or cold intolerance is unusual discomfort felt by some people when in a cool environment.There is much variation in the sensitivity to cold experienced by different people, with some putting on many layers of clothing while others in the same environment feel comfortable in one layer.Cold sensitivity may be a symptom of hypothyroidism, anemia, fibromyalgia or vasoconstriction. Vitamin B12 deficiency usually accompanies cold intolerance as well. There are other conditions that may cause a cold intolerance, including low body weight, high body temperature and low blood pressure. There may also be differences in people in the expression of uncoupling proteins, thus affecting their amount of thermogenesis. Psychology may also play a factor in perceived temperature. See also
Apparent temperature
Thermoception
Raynaud syndrome


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