Cyproheptadine Blockade of a Cardiogenic Hypertensive Chemoreflex

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Abstract
A cardiac chemoreceptor can be activated by serotonin [5-hydroxytryptamine] to cause a complex autonomic reflex which includes acute hypertension, changes in cardiac contractile force, and alteration of rhythm and conduction. In 16 anesthetized dogs blood pressure, heart rate and contractile force (Walton-Brodie strain gauges sutured on atria and ventricles) were continuously measured during serotonin-induced reflexes before and after i.v. administration of cyproheptadine and/or methysergide or morphine. Cyproheptadine in concentrations of 0.2-0.5 mg/kg attenuated the reflex responses, and higher concentrations (1.0 mg/kg) abolished the reflex (9 of 10 dogs). The responses to right stellate ganglion stimulations before and after cyproheptadine were identical, indicating that cyproheptadine had no effect on neural release of norepinephrine nor any significant .beta.-receptor blocking action. Cyproheptadine blockade was readily surmounted by a 10-fold increase in serotonin concentration. The serotonin reflex progressively recovered in time after the administration of cyproheptadine. CNS depression accounting for this abolishing effect of cyproheptadine is unlikely because of the surmounting effects of larger concentrations of serotonin. Methysergide and morphine had no significant effect in preventing the serotonin reflex. Cyproheptadine most likely interferes with the effect of serotonin at the site of initiation of the reflex within the cardiac chemoreceptor.

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