Ki: 82 nM for bovine brain A1 adenosine receptor

Proxyphylline is an A1 adenosine receptor antagonist.

The A1 adenosine receptor, the best characterized purinergic receptor family, can mediate responses via multiple pertussis toxin-sensitive GTP binding proteins to various different effectors.

In vitro: Previous study showed that proxyphylline could selectively antagonize A1 adenosine receptors versus A2 adenosine receptors (Ki = 850 μM for platelets) [1].

In vivo: In a previous study, rats that were allodynic following the vincristine injections were randomly allocated into four groups. Theoesberiven F (a combination of proxyphylline and Melilotus extract) was administered to rats. Results showed that the decreased paw withdrawal threshold induced by vincristine injection was increased by theoesberiven F treatment and the increased withdrawal frequency to cold stimuli was also reduced by theoesberiven F treatment [2].

Clinical trial: The proxyphylline PK was measured in healthy adults after intravenous, single oral and multiple oral doses to produce steady state. The mean peak time after oral administration was 29 min. The apparent volume of distribution was 0.611/kg. The ranges of biological half-life were 8.1-12.1 h and 8.3-12.6 h calculated from serum and urine data, respectively. In additioin, 24% of the dose was excreted in urine, which agreed with the relationship between the calculated total body clearance and the renal clearance of the drug [3].

References:
[1] U.  Schwabe, D. Ukena and M. J. Lohse. Xanthine derivatives as antagonists at A1 and A2 adenosine receptors. Naunyn-Schmiedeberg's Arch.Pharmacol. 330,212-221 (1985).
[2] S.  Bang, Y. S. Kim and S. R. Jeong. Anti-allodynic effect of theoesberiven F in a vincristine-induced neuropathy model. Exp. Ther. Med. 12(2), 799-803 (2016).
[3] Selvig K.  Pharmacokinetics of proxyphylline in adults after intravenous and oral administration. Eur J Clin Pharmacol. 1981 Jan;19(2):149-55.