TABLE 1.

Potency of xanthine derivatives as adenosine receptor antagonists in vivo in rats

Drug	Heart rate		Blood pressure		Ratio
	mg/kg	μmol/kg	mg/kg	μmol/kg
Caffeinea	3.39	17.5	3.63	18.7	1.07
Enprofyllinea	14.5	63.6	17.0	74.6	1.17
8-Phenyltheophyllinea	0.062	0.22	0.041	0.14	0.66
8-p-Sulphophenyltheophyllinea	0.85	2.3	1.71	4.70	2.01
XCCb	0.50	1.1	0.69	1.5	1.38
XACb	0.060	0.14	1.18	2.8	20

Results are expressed as the doses of the xanthine derivatives that produce a dose ratio of 2 for N-5′-ethylcarboxamidoadenosine (NECA). The control EC₅₀ for NECA ranged between 1.18 and 3.1 μg/kg (blood pressure) and 1.8 and 6.1 μg/kg (heart rate). Caffeine was tested in a single dose of 20 mg/kg. enprofylline in a dose of 10 mg/kg. and 8-phenyltheophylline and 8-p-sulphophenyltheophylline in a dose of 2 mg/kg. The Hill coefficients for the NECA dose–effect curves were as follows (blood pressure/heart rate; mean and 95% confidence interval): control—0.78 ± 0.16/1.03 ± 0.15; caffeine—1.09 ± 0.13/1.19 ± 0.12; enprofylline—0.73 ± 0.13/1.06 ± 0.07; 8-phenyltheophylline—0.69 ± 0.15/0.62 ± 0.26; and 8-p-sulphophenyltheophylline—0.55 ± 0.06/0.79 ± 0.14. The fact that the Hill coefficients were sometimes different from unity probably indicates that the slope of the dose–response curve was significantly affected by factors other than the drug–receptor interaction. XCC, 8-(4′-carboxymethyloxyphenyl)-1,3-dipropylxanthine; XAC. 8-(4′-carboxymethyloxyphenyl)-1,3-dipropylxanthine-2-aminoethylamide.

^aCalculated from: antilog [log (xanthine) − log (DR − 1)] (see Methods).

^bCalculated from Schild plot (Fig. 2).