Alpha-2 adrenergic receptor agonists
α2 adrenergic receptor agonists are clonidine, xylazine, Detomidine, Medetomidine and Romifidine are discussed here-
Clonidine
Clonidine is a partial α2 – adrenergic receptor agonist. Rapid IV injection causes a transient increase in BP due to activation of post junctional α2 receptors in peripheral vascular smooth muscles. However, this effect is followed by a more sustained hypotensive responsive mediated through activation of presynaptic α2 adrenoceptors in the lower brain stem (vasomotor centre in medulla oblongata), that causes decrease in central sympathetic outflow.
In CNS α2 receptors regulate the neuronal release of noradrenaline and several other transmitters and involved in the modulation of sympathetic outflow and cardiovascular and endocrine functions. In addition to central effects clonidine activates the prejunctional α2 receptors that suppress release of noradrenaline from peripheral nerve endings. Clonidine also stimulates parasympathetic outflow, which produces the bradycardia.
In addition to the CVS effect, clonidine produces other effects like: central sedative and analgesic effect, contraction of pregnant uterus leading to premature labour, inhibition of insulin and rennin secretion, stimulation of growth hormone, elevation of blood glucose level and activation of salt absorption from gut mucosa.
Clinical use of Clonidine
Clonidine is widely used in humans for treatment of hypertension. Also used for treating persons addicted to narcotics, alcohol and tobacco.
Xylazine
Xylazine is structurally related to clonidine and is a α2– receptor agonist. It is primarily used as a central sedative- analgesic with muscle relaxant properties.
Mechanism of action of Xylazine
α2-receptor activation produces analgesia and sedation similar to the of opioid receptor stimulation in the CNS. Both the receptors are found in similar region of the brain and on some of the same neurons.
Even though the receptors are different, both α2 and opioid receptors are connected to the same signal transducer and both types use the same effector mechanism. Hence when xylazine binds to α2 receptors, it causes activation of membrane associated G- proteins. This inturn opens potassium channels in the neuronal membrane , making the cell membrane hyperpolarized. Thus the neuronal cells become insensitive to exciting input and, the transmission pathway blocked. This finally results in sedation and analgesia .
Xylazine like clonidine also stimulates the prejunctional α2 receptors in peripheral synopsis and decrease the release of nor adrenaline.
Pharmacological effects of Xylazine
Xylazine on CNS– it produces sedation, analgesia, muscle relaxation and anxiolysis. in cats it causes emesis. Xylazine depresses thermoregulatory mechanisms and may produce either hypothermia or hyperthermia depending on the ambient temperature.
Xylazine on CVS– It produces transient hypertension, followed by longer lasting hypotension and decreased COP.
Clinical uses of Xylazine
Xylazine is Sedative, preanesthetic sedative prior to general anesthesia (inhalation or injectable) local anesthesia, as a general anesthetic in combination with ketamine, as emetic in cats.
Other selective α2-receptor agonists
Detomidine, Medetomidine, Romifidine (These are mostly in veterinary practice as anaesthetics, analgesics like xylazine) etc.