1972 Volume 19 Issue 1 Pages 11-22
The changes of blood pressure response produced by repeated administration of tyramine was investigated in morphine and pentobarbital anesthetized and atropinized dogs. Tyramine causes gradual attenuation of the pressor effect with repeated administration of doses of 0.5 to 1 mg/kg. A definite tachyphylaxis was obtained only with repeated administration of a large dose of tyramine in total doses averaging about 60 mg/kg. The tendency to cause tachyphylaxis of tyramine was more mild than that of ephedrine-like drugs (ephedrine, methamphetamine and pheniprazine). When the pressor effect was somewhat attenuated through repeated administration of tyramine, the pressor effect action of ephedrine-like drugs was slightly reduced. After the definite tachyphylaxis produced by tyramine, administration of ephedrine-like drugs caused a very small or no pressor effect. Sometimes only a slight fall of blood pressure was observed. On the other hand, after tachyphylaxis due to ephedrine-like drugs, the pressor effect in response to tyramine was suppressed considerably. The attenuated pressor effect after repeated dose of tyramine was restored to some extent towards the control pressor effect after about 1 / 2 to 1 hr intervals injections or norepinephrine infusion following the last administration of tyramine. However, if some dose of ephedrine-like drugs was administered during repeated administration of tyramine, the attenuated pressor effect of tyramine was not restored after the above-mentioned intervals. But it was restored slightly to some height after norepinephrine infusion. After tyramine tachyphylaxis the pressor effect to norepinephrine was observed in a normal and sufficiently intense rise. From these observations, it is most likely that the mechanism for producing tyramine tachyphylaxis is different from that of ephedrine-like drugs and primarily correlates with the entrance and accumulation of sufficient dose of tyramine into “labile store”. This replaces norepinephrine in the store, althrough tyramine may not readily bind as easily as ephedrine-like drugs.
