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The effect of oral nafazatrom (Bay g6575, 2 X 3 g) or placebo on inhaled antigen challenge was assessed in a double-blind study. In four subjects antigen challenge resulted in an immediate fall of 93.2 +/- 3.36% in airflow at 40% of vital capacity (Vp40) and a 45.85 +/- 4.95% reduction in forced partial expiratory volume at one second (FEV1). Neither nafazatrom nor placebo had any effect on baseline lung function or that after challenge. Leukotriene B4 was generated by ex vivo stimulus of blood with ionophore A23187, and quantified by high performance liquid chromatography (h.p.l.c.)-radioimmunoassay. No inhibition of LTB4 formation occurred ex vivo following oral nafazatrom, although addition of 10(-5) M nafazatrom to blood in vitro significantly inhibited LTB4 release. Peak plasma nafazatrom levels during the study ranged from 3.3 X 10(-7) M to 1.47 X 10(-6) M which are below the concentration (10(-5) M) at which significant 5-lipoxygenase inhibition occurs in vitro. Oral nafazatrom is ineffective as a 5-lipoxygenase inhibitor in man, probably because of poor bioavailability after administration.

1 The efficacy of labetalol in lowering blood pressure has been assessed in a group of 16 patients with severe hypertension whose blood pressure was inadequately controlled (supine diastolic blood pressure greater than 110 mmHg on two consecutive occasions) on existing therapy or in whom severe side-effects necessitated a change in therapy. 2 All patients had an original pretreatment supine diastolic blood pressure of greater than 120 mmHg and most had evidence of target organ damage. Patients were hospitalized for the purposes of changeover of therapy, labetalol being added to the existing regime which was reduced stepwise and eventually withdrawn. 3 Treatment with labetalol resulted in satisfactory blood pressure control in 10 of 16 patients in this study but high doses were required, the mean daily dose being 3,091 mg (range 1,200-8,000). 4 Treatment with discontinued in 6 patients on account of postural hypotension (3), failure to control supine diastolic blood pressure (2) and retention of urine (1). Long-term treatment was relatively free from side-effects. 5 From preliminary studies in animals it is suggested that an action within the central nervous system may contribute to the hypotensive effect of labetalol.