A triazolopyrazine (ICI 58 301) and a triazolopyrimidine (ICI 63 197), both potent inhibitors of 3'5'-cyclic adenosine monophosphate phosphodiesterase, protected conscious guinea-pigs against an otherwise lethal bronchospasm caused by inhalation of histamine. Both compounds were active when given by mouth and the activity was both rapid in onset and persistent. Bronchospasm caused by histamine or acetylcholine in guinea-pig isolated lungs was reduced when the lungs were perfused with dilute solutions of the compounds and the bronchodilator activity of catecholamines was potentiated.In anaesthetized animals the compounds were relatively more active against severe bronchospasm than against milder stimuli. The antibronchoconstrictor effects on conscious guinea-pigs were blocked by propranolol but not by practolol even in much larger doses. Propranolol did not, however, block the effect on the isolated lung. It appears possible that the antibronchoconstrictor activity is a manifestation of the inhibition of phosphodiesterase.A study of the pharmacological properties of purine isosteres, made in these laboratories during the past 15 years has revealed that two series of compounds, triazolopyrazines and triazolo-pyrimidines are particularly potent inhibitors of bronchospasm in guinea-pigs. The representatives of these series now discussed are 3-acetamido-6-methyl-8-n-propyl-s-triazolo [4,3-a] (Dukes, 1971). ICI 58 301 will be referred to as A and ICI 63 197 as B.

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1 fl-adrenoceptor blockade, plasma labetalol concentrations and anti-hypertensive actions were investigated at 2 hourly intervals during the interdose period of chronic oral therapy in six hypertensive patients.2 f,-adrenoceptor blockade varied during the inter-dose period and was maximal 2 and 4 h after the oral dose (P < 0.05). 3 Systolic pressure rose during the interdose period (P < 0.05). A significant correlation was found between the degree of fl-adrenoceptor blockade and the change in systolic pressure at 2 h after the oral dose.4 Efficacy of labetalol as a P-adrenoceptor antagonist and anti-hypertensive drug was assessed 2 h after an oral dose during chronic eight hourly dosage in sixteen hypertensive patients. Pharmacokinetics of labetalol were studied in the same patients. 5 Peak plasma labetalol concentration occurred 2 h after the oral dose and subsequently the plasma concentration declined monoexponentially.6 The steady state concentration (Css) of labetalol was correlated significantly with the daily oral dose in mg kg , the mid point labetalol concentration (Cmax + Cmin) and the isoprenaline dose ratio-I 2 at 2 h after the oral dose.7 No correlation was found between the antihypertensive effect and the Css ng ml-1 labetalol or between the isoprenaline dose ratio-I and the Css labetalol ng ml-.