Dissociation of norepinephrine turnover from alpha-2 responses after clorgiline.
Responses to intravenous clonidine, a possible central noradrenergic probe, were examined in patients with depression before and after treatment with clorgiline, a selective monoamine oxidase type A inhibitor. Pulse rate, mean arterial blood pressure, plasma norepinephrine, 3-methoxy-4-hydroxyphenylglycol, and growth hormone were measured. Clorgiline treatment (2.5 to 10 mg/day) produced a variable reduction in the hypotensive response to clonidine but did not influence heart rate or plasma norepinephrine responses. Clorgiline markedly reduced the urinary output of norepinephrine and metabolites, indicating a reduced turnover of norepinephrine. None of the measured parameters corresponded with clinical effect. These data suggest that any clorgiline-induced alterations in alpha 2-receptor function as measured by responses to clonidine are modest and highly variable. Furthermore, since the variable and inconsistent changes in alpha 2-receptor function are dissociated from the massive changes in norepinephrine metabolism, regulation of presynaptic alpha 2-receptors appears unlikely to mediate the effects of clorgiline in patients with depression.
Hauger
R L
RL
Veterans Administration Medical Center, La Jolla, Calif.
Scheinin
M
M
Siever
L J
LJ
Linnoila
M
M
Potter
W Z
WZ
D001714:Bipolar Disorder / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine; D003010:Clorgyline / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D011437:Propylamines / Q000627:therapeutic use*; D011674:Pulse / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology
D011437:Propylamines; D011942:Receptors, Adrenergic, alpha; D008734:Methoxyhydroxyphenylglycol; D013006:Growth Hormone; D003010:Clorgyline; D003000:Clonidine; D009638:Norepinephrine