Depletion of S-adenosyl-L-methionine in mouse brain by antidepressive drugs.

A sensitive enzymatic-isotopic method based on the methylation of histamine by histamine methyltransferase has been used to measure the endogenous concentration of S-adenosyl-L-methionine in mouse brain. After a single dose of imipramine, DL-dopa, pargyline or d-amphetamine, brain S-adenosyl-L-methionine levels were 50% depleted after 1 hour, but had returned to normal values within 4 hours after drug treatment. A similar but long-lasting depletion of S-adenosyl-L-methionine was obtained after chronic treatment with imipramine or after a single dose of cycloleucine, a drug that interferes with the synthesis of S-adenosyl-L-methionine from methionine. The rate of methylation of 3H-norepinephrine given by intraventricular injection suggested that the decreased levels of S-adenosyl-L-methionine after the administration of cycloleucine and after the chronic, but not the acute, administration of imipramine may interfere with the inactivation of norepinephrine in the mouse brain. These results indicate that decreased methylation may contribute to the neurochemical effects of antidepressive drugs.