Promethazine affects autonomic cardiovascular mechanisms minimally

J Pharmacol Exp Ther. 1997 Aug;282(2):839-44.


Promethazine hydrochloride, Phenergan, is a phenothiazine derivative with antihistaminic (H1), sedative, antiemetic, anticholinergic, and antimotion sickness properties. These properties have made promethazine a candidate for use in environments such as microgravity, which provoke emesis and motion sickness. Recently, we evaluated carotid baroreceptor-cardiac reflex responses during two Space Shuttle missions 18 to 20 hr after the 50 mg intramuscular administration of promethazine. Because the effects of promethazine on autonomic cardiovascular mechanisms in general and baroreflex function in particular were not known, we were unable to exclude a possible influence of promethazine on our results. Our purpose was to determine the ground-based effects of promethazine on autonomic cardiovascular control. Because of promethazine's antihistaminic and anticholinergic properties, we expected that a 50-mg intramuscular injection of promethazine would affect sympathetically and vagally mediated cardiovascular mechanisms. Eight healthy young subjects, five men and three women, were studied at rest in recumbency. All reported drowsiness as a result of the promethazine injection; most also reported nervous excitation, dry mouth, and fatigue. Three subjects had significant reactions: two reported excessive anxiety and one reported dizziness. Measurements were performed immediately prior to injection and 3.1 +/- 0.1 and 19.5 +/- 0.4 hr postinjection. We found no significant effect of promethazine on resting mean R-R interval, arterial pressure, R-R interval power spectra, carotid baroreflex function, and venous plasma catecholamine levels.

Publication types

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

MeSH terms

  • Adult
  • Antiemetics / adverse effects
  • Antiemetics / pharmacology*
  • Antiemetics / therapeutic use
  • Autonomic Nervous System / drug effects*
  • Autonomic Nervous System / physiopathology
  • Baroreflex / drug effects
  • Blood Pressure / drug effects
  • Cardiovascular System / drug effects*
  • Cardiovascular System / innervation
  • Catecholamines / blood
  • Female
  • Humans
  • Male
  • Promethazine / adverse effects
  • Promethazine / pharmacology*
  • Promethazine / therapeutic use
  • Reference Values
  • Space Motion Sickness / physiopathology
  • Space Motion Sickness / prevention & control


  • Antiemetics
  • Catecholamines
  • Promethazine