Three new angiotensin converting-enzyme inhibitors were given orally to 20 men in single doses ranging from 1.25 to 40 mg. Two of them induced comparable marked inhibition of both the blood pressure response to exogenous angiotensin I and plasma converting-enzyme activity. Onset of action was relatively slow, but 21 to 24 hr after drug plasma converting-enzyme activity was still clearly reduced. The third was less active. There was a close correlation between blood pressure response on administration of angiotensin I and plasma converting-enzyme activity. There were no adverse effects. These new drugs are interesting because of their long duration of action. The measurement of plasma converting-enzyme activity seems useful for monitoring efficacy of converting-enzyme blockade and compliance to therapy.

Human blood platelets incubated for one hour at 37° C. with dopamine-l-HC (DA) accumulated the amine against a gradient. Such accumulation was markedly reduced by cold and by various metabolic inhibitors including iodoacetate, dinitrophenol, and sodium cyanide. Increasing the concentration of DA caused a decrease in the steady-state distribution ratio which suggests that the uptake process is saturable. Various compounds which inhibit or compete for the amine pump in the platelet membrane, including desmethylimpromine (DMI), diphenhydramine, serotonin, debrisoquin, and guanethidine, depress the accumulation of DA. Uptake of DA was also reduced by benztropine, trihexyphenidyl, and haloperidol. Less than 10 per cent of the DA which accumulates in the platelet during one hour is metabolized.DA is a relatively poor substrate for platelet MAO and in addition the cell does not appear to contain dopamine f3-hydroxylase.

The Heidelberg capsule is an indigestible indicator of gastrointestinal pH, which was used to evaluate the relationship between gastric residence time (GRT) and variability in aspirin absorption from enteric-coated tablets. In a crossover study, eight healthy subjects (four men and four women) received an enteric-coated aspirin (648 mg) together with a Heidelberg capsule while fasting or with food (breakfast, followed 4 hours later by lunch). Salicylic acid and salicyluric acid concentrations in plasma and urine were measured by HPLC. The mean (+/- SD) GRT was significantly delayed by food (0.8 +/- 0.5 vs. 5.9 +/- 3.3 hours; P less than 0.005). The mean (+/- SD) lag time (TL) and time to peak concentration (expressed as salicylic acid equivalents) were markedly prolonged after the fed regimen (2.7 +/- 0.8 vs. 8.9 +/- 3.7 hours [P less than 0.005] and 8.3 +/- 2.9 vs. 13.8 +/- 4.5 hours [P less than 0.025]). For the combined data from the fasting and fed evaluations, an excellent correlation existed between TL and GRT of the capsule (TL = 1.0 GRT + 1.95; n = 16; r = 0.94; P less than 0.0001). Women demonstrated greater delays in GRT and TL than did men. The delay in aspirin absorption from an enteric-coated tablet is directly related to its GRT, which is gender related and greatly affected by food.

The uptake and release of norepinephrineThe uptake of norepinephrine (NE)