Possible Interaction: Adenosine and Diazepam

“ Diazepam inhibits phosphodiesterase type 4 and enhances the effect of some 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent positive inotropic drugs.”

“In order to reveal the possible role of inhibition of membrane adenosine transport in the effects of diazepam (a moderate inhibitor of membrane adenosine transport), the action of a 10-day treatment with dipyridamole or S-(p-nitrobenzyl)-6-thioinosine (NBTI; prototypic adenosine uptake inhibitors) was also studied.”

“…,diazepam (… adenosine on indirect twitch responses 3 The central type receptor agonist, clonazepam did not affect the inhibitory effect of adenosine 4 The peripheral benzodiazepine receptor … benzodiazepines potentiate the adenosine‐effected presynaptic inhibition of neuromuscular transmission by an inhibition of adenosine uptake through activation of peripheral type benzodiazepine receptors.”

“ Diazepam … adenosine ; the maximal contractile effect of adenosine (% vs. acetylcholine 10(-3) M) was 20.4 +/- 4.2 (n = 21) in control conditions and 45.5 +/- …(-7) to 10(-5) M), both agonists of peripheral benzodiazepine receptors, potentiated the contractile effects of adenosine to the same extent as diazepam.”

“Dipyridamole (10−5 M) and diazepam (10−4 M) respectively produced a 56.2 and 32.4‐fold potentiation of adenosine relaxant effects.”

“Added to the superfusion medium diazepam blocked responses to adenosine but not 5-HT; this effect was not observed with 2-chloroadenosine or in the presence of 2-hydroxynitrobenzylthioguanosine.”

“In a concentration (30 microM) virtually devoid of an effect on the …, twitch responses, or resting membrane potential of the muscle fibres, diazepam potentiated … adenosine on neuromuscular transmission, but not that induced by the stable analogue of … adenosine (NECA), which is not a substrate for the adenosine uptake system.”

“The results suggest that diazepam acts at the frog neuromuscular junction by increasing the level of adenosine at the junction level; this increase probably results from inhibition in the uptake of the nucleoside.”

“The inhibitory effect of adenosine but not that of 2-chloroadenosine was potentiated in the presence of diazepam.”

“ Diazepam tended to potentiate negative chrono- and inotropic effects of adenosine but not significantly, suggesting that diazepam plays a minor role as an adenosine potentiator in the dog right atrium.”

“ Adenosine (10(-6) M) and ATP (10(-6) M) were degraded to inactive inosine during incubation with atrial segments and their degradation was inhibited by diazepam.”