Adenosine mechanisms are not affected by antidepressant concentrations of desipramine.
We have evaluated the proposal that adenosine may mediate some of the effects of tricyclic antidepressant therapy. In-vitro desipramine (DMI) (1-10 microM) did not affect adenosine or 2-chloroadenosine-induced inhibition of lipolysis or the adenosine stimulated formation of cyclic (c) AMP in the hippocampal slice. However, very high concentrations of desipramine (0.2-0.5 mM) as well as some detergents potentiated the stimulatory effect of adenosine on cAMP formation. The ATP, ADP and AMP contents in slices were unaffected as was the electrically evoked release of purines. Long-term treatment in-vivo with antidepressants in clinically relevant doses did not alter the sensitivity of adenosine receptor mediated cAMP formation in-vitro while the beta-adrenoceptor-mediated formation was depressed by desipramine or imipramine treatment but not by zimelidine or fluoxetine treatment. It is concluded that actions on central adenosine mechanisms are unlikely to play any important role in the therapeutic effects of tricyclic antidepressants.
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D004558:Electric Stimulation; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009711:Nucleotides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000928:Antidepressive Agents; D009711:Nucleotides; D000242:Cyclic AMP; D000241:Adenosine; D003891:Desipramine; D009638:Norepinephrine