Dexmedetomidine: CNS effects

Dexmedetomidine is a unique sedative-analgesic. Since its approval by the FDA in 1999, the prevalence in the hospital and indications for use have expanded. It’s mechanism of action is by presynaptic alpha 2-adrenoreceptor agonism. This results in the inhibition of release of norepinephrine and thus cause analgesia. Alpha 2 adrenoreceptors exist both in the spinal cord and supraspinal. Peripheral adrenoreceptors are also thought to play a role in the antinociceptive properties of Dexmedetomidine. The activation of inwardly rectifying G1-protein gated potassium channels results in membrane hyperpolarization and decreased rate of firing of excitable cells.

While we do not yet have a comeplte understanding of Dexmedetomidine, one hypothesis is that it primarily acts in the locus coeruleus. The locus coeruleus has the highest density of alpha 2 receptors and thus is attributed to the sedative and hypnotic effects of Dexmedetomidine. Opioidergic systems have common effector mechanisms in the medullospinal noradrenergic pathway, which may be responsible for the synergism of Dexmedetomidine and opioids and indicate a supraspinal mechanism for the drug. Though Dexmedetomidine has also been shown to inhibit firing of nociceptive neurons in the spinal cord, this is not thought to be the primary mechanism of action.