Enhanced signal transduction by adenylate cyclase in platelet membranes of patients showing antidepressant responses to alprazolam: preliminary data.
The triazolobenzodiazepine, alprazolam, was administered to 11 depressed patients over a period of six weeks, and six patients showed a favorable antidepressant response. There were no significant differences between responders and nonresponders in age, pretreatment Hamilton Depression Rating Scores, 4 p.m. postdexamethasone plasma cortisol levels, or platelet monoamine oxidase activities. Blood levels of alprazolam were not meaningfully different in responders and nonresponders when measured on treatment day 8. However, on treatment day 8, significantly enhanced prostaglandin D2-stimulated platelet adenylate cyclase activity, greater suppression of prostaglandin D2-stimulated platelet adenylate cyclase activity by epinephrine, and enhanced sodium fluoride-stimulated platelet adenylate cyclase activity were seen in the six patients who went on to respond to alprazolam, but not in the five nonresponders. In contrast, there were no significant changes in prostaglandin D2, (-)-isoproterenol, or fluoride ion-stimulated leukocyte adenylate cyclase activity in responders or nonresponders. No meaningful changes were observed in the mean densities of either the high-affinity platelet alpha 2-adrenergic receptor (for 3H-p-aminoclonidine) or the leukocyte beta-adrenergic receptor (for 3H-dihydroalprenolol) in responders or nonresponders. The present findings, taken in conjunction with findings from other recent studies, suggest that enhanced coupling between certain neurotransmitter or hormone receptors and adenylate cyclase through the guanine nucleotide regulatory proteins may help explain the antidepressant effects of alprazolam and possibly other forms of antidepressant treatment.
Mooney
J J
JJ
Schatzberg
A F
AF
Cole
J O
JO
Kizuka
P P
PP
Schildkraut
J J
JJ
D000262:Adenylyl Cyclases / Q000097:blood*; D000328:Adult; D000368:Aged; D000525:Alprazolam; D000928:Antidepressive Agents; D001569:Benzodiazepines / Q000627:therapeutic use*; D001792:Blood Platelets / Q000201:enzymology*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011942:Receptors, Adrenergic, alpha / Q000032:analysis; D011943:Receptors, Adrenergic, beta / Q000032:analysis
D000928:Antidepressive Agents; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D001569:Benzodiazepines; D000262:Adenylyl Cyclases; D000525:Alprazolam