Early Studies on Opioid Drug-Induced Release of Histamine

2 Early Studies on Opioid Drug-Induced Release of Histamine 

In 1907 Windaus and Vogt completed the first chemical synthesis of histamine and soon after Sir Henry Dale and coworkers began investigations that showed that histamine was a powerful vasodepressant, it stimulated smooth muscle from the gut and respiratory tract and caused shock when injected into laboratory animals mimicking the systemic effects of anaphylaxis. These early results were followed by demonstration of the involvement of histamine in vascular reactions of the skin and the observation that morphine caused the so-called triple response in human skin, that is, the event sequence of an initial red spot followed by a red irregular flare and a fluid-filled wheal. Over 30 years later antihistamines were shown to reduce morphine-induced skin wheals, and histamine itself was detected in effluents of isolated perfused cat gastrocnemius muscle after arterial injection of opium alkaloids. Released histamine was also detected in cat skin, and raised levels were found in plasma after intravenous injection of morphine. 

The significance of the release of histamine in humans stems from its actions of increasing both heart rate and the force of myocardial contraction, thus increasing cardiac output, and from its dilatator effect on small blood vessels that leads to flushing, decreased vascular resistance, and 

Challenge agent Time (min) to reach peak histamine level Range of histamine levels (ng/ml) Time (min) to return to baseline  

Results summarized from McBride P et al. J AUeigy Qin Immunol. 1989 83 374 

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