An alternative approach involves the use of agents which combine
these properties such as the methylxanthine derivatives, pentoxifylline
(oxpentifylline), pentifylline and propentofylline. These
agents have mixed actions; they (i) inhibit cAMP- and cGMPphosphodiesterases
(thereby increasing the intracellular concentrations
of these calcium-regulating cyclic nucleotides), (ii) block
the adenosine transporter thereby preventing adenosine uptake
and increasing adenosine levels (Andine 1990), and (iii) block
phospholipase (Ward 1987). Additionally, propentofylline has
been shown to increase brain GABA concentrations (Vukadinovic
1986) and reduce glutamate release under ischaemic conditions
(Andine 1990;Miyashita 1992). As a result of the above, methylxanthine
derivatives are vasodilators, inhibit platelet aggregation
and thromboxane A2 synthesis, inhibit phagocyte function (e.g.
decrease the release of free radicals), increase prostacyclin synthesis
from endoperoxides, reduce blood viscosity through increasing
erythrocyte flexibility, decreasing erythrocyte aggregation and
reducing plasma fibrinogen concentration (Ott 1983), and may
be neuroprotective (Ward 1987) as adenosine inhibits glutamate
release. Pentoxifylline has been shown to increase cerebral blood
flow in patients with acute stroke (Hartmann 1986). Ischae