Central alpha 1-adrenoceptor stimulation functionally antagonizes the hypnotic response to dexmedetomidine, an alpha 2-adrenoceptor agonist

Anesthesiology. 1991 Aug;75(2):252-6. doi: 10.1097/00000542-199108000-00013.


Previously, we demonstrated that dexmedetomidine, an alpha 2 agonist, produces a hypnotic-anesthetic response in rats via activation of central alpha 2 adrenoceptors and that this response could be enhanced by the alpha 1 antagonist prazosin. In the current experiment we investigated whether central alpha 1 adrenoceptor stimulation antagonizes the alpha 2 adrenoceptor-mediated hypnotic response. Cirazoline, an alpha 1 adrenoceptor agonist that partitions into the central nervous system, attenuated dexmedetomidine's hypnotic response whether administered systemically (0.3-1 mg.kg-1 intraperitoneally [ip]) or centrally (0.1 mg.kg-1 intracerebroventricularly). Prazosin, an alpha 1 adrenoceptor antagonist that effectively crosses the blood-brain barrier, fully blocked cirazoline's attenuating effect on dexmedetomidine-induced hypnosis, whereas doxazosin, which partitions poorly into the brain, did not block cirazoline's effect. Administration of phenylephrine, 0.3-3 mg.kg-1 ip, an alpha 1 adrenoceptor agonist that does not penetrate into the brain, did not attenuate dexmedetomidine's hypnotic effect. These results indicate that central alpha 1-adrenoceptor stimulation functionally antagonizes the hypnotic response to an alpha 2-adrenoceptor agonist. These data underscore the important requirement for alpha 2 adrenoceptor selectivity if these agonists are to be useful in the anesthetic setting.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Drug Interactions
  • Imidazoles / administration & dosage
  • Imidazoles / antagonists & inhibitors
  • Imidazoles / pharmacology*
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Male
  • Medetomidine
  • Phenylephrine / pharmacology
  • Prazosin / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects*
  • Sleep / drug effects*


  • Adrenergic alpha-Agonists
  • Imidazoles
  • Receptors, Adrenergic, alpha
  • Phenylephrine
  • Medetomidine
  • cirazoline
  • Prazosin