Mechanism of the Cardiovascular Actions of Cyclocytidine

Summary

The clinical usefulness of cyclocytidine, an otherwise potentially valuable antineoplastic agent, is limited because it may cause acute postural hypotension in man. In the laboratory, cyclocytidine (5-100 mg/kg) transiently increased blood pressure in anesthetized dogs, cats and rats. As the pressor responses to cyclocytidine were prevented by previous treatment with 6-hydroxydopamine or acutely by phentolamine, guanethidine and desmethylimipramine, but not by hexa-methonium, adrenergic nerve terminals appear to be involved in its pressor actions. Cyclocytidine also blocked pressor responses to tyramine and caused intolerance to tilt stress in anesthetized dogs. Cyclocytidine thus appears to promote, then prevent, release of norepinephrine from adrenergic vasoconstrictor neurons.