Effect of long-term clorgyline administration on human platelet alpha-adrenergic receptor binding and platelet cyclic AMP responses

Platelet α₂-adrenergic receptor number and physiologic responsiveness, as well as plasma norepinephrine (NE), were evaluated in psychiatric patients with major depressive disorder before and during chronic clorgyline treatment. The α₂-adrenergic receptor number was determined by measuring the binding of tritiated dihydroergocriptine (³H-DHE) to platelet membranes. Physiologic responsiveness was determined by measuring the response of cyclic adenosine 3'-5' monophosphate (cAMP) to prostaglandin E₁ (PGE₁), and the inhibition of the PGE₁-stimulated cAMP response by NE in intact platelets. No significant differences from pretreatment values were observed in platelet α₂-adrenergic binding or responsiveness during clorgyline treatment. Baseline platelet cAMP production and plasma NE levels were significantly decreased after chronic clorgyline treatment. Previous studies on animals and humans have suggested that brain α₂-adrenergic receptor responsiveness decreases during chronic clorgyline treatment. The present findings therefore suggest that such changes may represent adaptations induced by long-term clorgyline administration which may differ between the brain and the platelet, thus illustrating potential limitations of the study of platelet α₂-adrenergic receptors as a model for central α₂-adrenergic receptor adaptation.