5'-Deoxy-5-iodotubercidin was previously reported to cause potent muscle relaxation and
hypothermia when injected i.p. into mice. In normotensive rats, i.v. injection reduced blood pressure and heart rate.
5-Iodotubercidin possessed the same in vivo activities whereas
tubercidin was pharmacologically almost inactive. None of these compounds interacted significantly with Al
adenosine receptors, as determined by their ability to displace 3H-N6-phenylisopropyladenosine or 3H-5'-N-ethylcarboxamidoadenosine bound to rat brain membranes. Furthermore these compounds were much weaker than
adenosine as agonists of
adenosine-stimulated
adenylate cyclase in guinea-pig brain slices (A2 receptors). A previous report showed that
5'-deoxy-5-iodotubercidin and
5-iodotubercidin were very potent inhibitors of
adenosine kinase from rat or guinea-pig brain and were potent inhibitors of 3H-adenosine uptake into brain slices; relative to the halogenated derivatives,
tubercidin was quite weak as an inhibitor of
adenosine kinase and of
adenosine uptake. We therefore propose that a significant part of the in vivo activity of the two halogenated
tubercidin analogues may not be due to a direct agonist action at A1 and/or A2
adenosine sites (as proposed for a number of other metabolically-stable analogues of
adenosine) but may result from an inhibition of reuptake of endogenously-released
adenosine; the increased extracellular levels of
adenosine resulting from this action could then interact directly with membrane receptors. Consistent with this, low concentrations of
5'-deoxy-5-iodotubercidin were shown to significantly potentiate the effects of exogenous
adenosine on blood pressure and heart rate in anaesthetized rats and on
adenosine-stimulated cAMP generation in guinea-pig brain slices. None of these compounds interacted with central
benzodiazepine receptors. The cardiovascular and behavioural effects of
5'-deoxy-5-iodotubercidin and
5-iodotubercidin were blocked by
theophylline; results from the cardiovascular studies suggest there may be different
adenosine receptors in heart and blood vessels.