Studies on the interrelationship between the syntheses of noradrenaline and metaraminol

Summary1 . Experiments were conducted to determine the influence of the rate of noradrenaline synthesis on the conversion of alpha‐methyl‐ m ‐tyrosine to metaraminol. 2 . Male Wistar rats, 175–200 g, were placed into four groups and treated with (1) alpha‐methyl‐ p ‐tyrosine methyl ester, 250 mg/kg (2) dl ‐alpha‐methyl‐ m ‐tyrosine, 400 mg/kg (3) alpha‐methyl‐ p ‐tyrosine methyl ester, 250 mg/kg plus dl ‐alpha‐methyl‐ m ‐tyrosine, 400 mg/kg or (4) an equivalent volume of injection vehicle. All solutions were injected intraperitoneally. 3 . Immediately after treatment half of the rats were transferred to 4° C with the remaining animals being kept at 27° C. 4 . The rats were killed 4, 8 and 12 h after injection, the brains, hearts, spleens and adrenals removed and analysed for adrenaline, noradrenaline, metaraminol and alpha‐methyl‐ m ‐tyramine. 5 . In virtually all cases, both during rest (27° C) and sympathetic stress (4° C), treatment of the rats with alpha‐methyl‐ p ‐tyrosine methyl ester increased the amount of metaraminol formed from alpha‐methyl‐ m ‐tyrosine. The only organ not containing increased quantities of metaraminol in the presence of alpha‐methyl‐ p ‐tyrosine methyl ester was the adrenals, taken from the rats kept at 27° C. Adrenals removed from the cold‐exposed rats contained more metaraminol when alpha‐methyl‐ p ‐tyrosine methyl ester was combined with alpha‐methyl‐ m ‐tyrosine than when alpha‐methyl‐ m ‐tyrosine was used alone. 6 . These results demonstrate that the inhibition of noradrenaline synthesis, by treatment with the tyrosine hydroxylase inhibitor alpha‐methyl‐ p ‐tyrosine methyl ester, increased the conversion of alpha‐methyl‐ m ‐tyrosine to metaraminol. It is concluded that inhibiting the formation of dopa allowed increased amounts of alpha‐methyl‐ m ‐tyrosine to enter the biosynthetic pathway. These results support the false sympathetic transmitter concept advanced for metaraminol.