Neuroendocrine and other studies of the mechanism of antidepressant action of desipramine.
It is not known whether in depressed patients antidepressant treatment increases or reduces monoaminergic neurotransmission. Clinical studies are therefore reviewed that investigate adaptive changes at adrenoceptors in depressed patients treated with desipramine, and the net effect of these changes upon neurotransmission. Although in animals chronic desipramine treatment enhances the responsiveness of alpha 1-adrenoceptors to phenylephrine, no such effect could be demonstrated in patients upon the responsiveness of pupil diameter to phenylephrine. However, in keeping with animal studies, clinical evidence of altered responsiveness of alpha 2-adrenoceptors could be demonstrated after chronic desipramine treatment. The alpha 2-mediated growth hormone response to clonidine was increased after one week's treatment with desipramine and then reduced during the second and third weeks of treatment. No clinical measure of the responsiveness of central beta-adrenoceptors is available. However, the secretion of melatonin is a measure of neurotransmission at noradrenergic terminals in the pineal with alpha 1-, alpha 2- and beta 1-adrenoceptors. In normal volunteers the secretion of melatonin was increased by the noradrenaline uptake inhibitors desipramine and (+)-oxaprotiline; (-)-oxaprotiline had no effect. In depressed patients melatonin secretion was increased after three weeks' treatment with desipramine. These and other clinical studies suggest that antidepressant treatments increase noradrenergic neurotransmission in depressed patients.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003863:Depression / Q000503:physiopathology*; D003891:Desipramine / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012636:Secretory Rate / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D013006:Growth Hormone; D008550:Melatonin; D003000:Clonidine; D003891:Desipramine; D014439:Tyramine