Among the mediators involved in the asthma bronchoconstriction and inflammation mechanisms, there is now substantial evidence that the sulfidopeptide leukotrienes (LTs) are important. Antagonists of their receptors and inhibitors of their synthesis have been developed.Antagonists of LTs, as well as inhibitors of their synthesis, reduce the LTs actions: bronchoconstriction, bronchial hyperresponsiveness, hypersecretion and inflammation. They produce an acute bronchodilating effect in mild asthma, reduce the hyperresponsiveness responses due to allergens, aspirin and cold and dry air, and also cutaneous and gastrointestinal reactions. Oral administrations tested during 4 or 6 weeks diminish the use of the beta-agonists, decrease the asthma symptom scores and other inflammatory signs.More studies for longer periods, double blind trials and comparisons with classical treatments will be necessary to define the real place of LTs antagonists in the treatment of asthma. So their efficacy has to be confirmed as well as their good tolerance profile (particularly for hepatic functions).Antagonists of receptors and synthesis inhibitors of LTs have known a recent and important development. They constitute a new therapeutic class: further studies are needed to better define the place of these new drugs in the treatment of asthma and other inflammatory diseases.

Objectives. - Among the mediators involved in the asthma bronchoconstriction and inflammation mechanisms, there is now substantial evidence that rite sulfidopeptides leukotrienes (LTs) are important. Antagonists of their receptors and inhibitors of their synthesis have been developed.Important points. - Antagonists of LTs, as well as inhibitors of their synthesis, reduce the LTs actions: bronchoconstriction, bronchial hyperresponsiveness, hypersecretion and inflammation. They produce an acute bronchodilating effect in mild asthma, reduce the hyperresponsiveness responses due to allergens, aspirin and cold and dry air, and also cutaneous and gastrointestinal reactions. Oral administrations tested during 4 or 6 weeks diminish the use of the beta-agonists, decrease the asthma symptom scores and other inflammatory signs,Perspectives and projects. - More studies for longer periods, double blind trials and comparisons with classical treatments will be necessary to define the real place of LTs antagonists ill the treatment of asthma. So their efficacy has to be confirmed as well as their good tolerance profile (particularly for hepatic functions.Conclusion. - Antagonists of receptors and synthesis inhibitors of LTs have known a recent and important development. They constitue a new therapeutic class: further studies are needed to better define the place of these new drugs br the treatment of asthma mid other inflammatory diseases. (C) 1998, Elsevier, Paris.

Among the mediators involved in the asthma bronchoconstriction and inflammation mechanisms, there is now substantial evidence that the sulfidopeptide leukotrienes (LTs) are important. Antagonists of their receptors and inhibitors of their synthesis have been developed.Antagonists of LTs, as well as inhibitors of their synthesis, reduce the LTs actions: bronchoconstriction, bronchial hyperresponsiveness, hypersecretion and inflammation. They produce an acute bronchodilating effect in mild asthma, reduce the hyperresponsiveness responses due to allergens, aspirin and cold and dry air, and also cutaneous and gastrointestinal reactions. Oral administrations tested during 4 or 6 weeks diminish the use of the beta-agonists, decrease the asthma symptom scores and other inflammatory signs.More studies for longer periods, double blind trials and comparisons with classical treatments will be necessary to define the real place of LTs antagonists in the treatment of asthma. So their efficacy has to be confirmed as well as their good tolerance profile (particularly for hepatic functions).Antagonists of receptors and synthesis inhibitors of LTs have known a recent and important development. They constitute a new therapeutic class: further studies are needed to better define the place of these new drugs in the treatment of asthma and other inflammatory diseases.

A number of fluoroquinolones have been shown to interact adversely with theophylline. We studied the influence of coadministration of temafloxacin, a new fluoroquinolone antimicrobial agent, on steady-state theophylline pharmacokinetics. Twelve healthy subjects (8 males, 4 females; average age and weight 34 years and 62 kg, respectively) were given oral controlled-release theophylline in an individualized dosage to achieve a target plasma level of 10 mg/L. Once steady state was achieved, temafloxacin 600 mg given orally twice daily was concomitantly administered for 4–5 days. Serial blood samples were collected before and during simultaneous temafloxacin administration and plasma assayed for theophylline using a high-performance liquid chromatography technique. Theophylline pharmacokinetic parameters were determined noncompartmentally, and results of single and combined administration were compared. Theophylline plasma concentrations did not differ significantly with temafloxacin coadministration, and similar area-under-the-curve (AUC) values were observed. Theophylline oral clearance increased from 2.67 ± 1.01 L/hour to 2.69 ± 0.93 L/hour, when given alone and with temafloxacin, respectively (p = 0.92). Only 2 of 12 subjects showed an appreciable decrease in clearance when theophylline and temafloxacin were administered together, while 2 subjects demonstrated increases >15% and 8 showed no change. We conclude that temafloxacin does not interact significantly with theophylline and that these agents can be safely administered together.

The effects of atropine, 2 mg/kg i.v., on anaphylactic shock were studied in guinea-pigs sensitized to ovalbumin.

The effects of metiamide and of four H1 receptor blocking agents (mepyramine, promethazine, clemastine and ketotifene) on anaphylactic reaction were studied in the guinea-pig. The H1 blockers conferred partial protection which shows that with the experimental protocol utilized (challenge injection with high doses of antigen), histamine plays a lesser role than other mediators released or synthesized. Metiamide (30.0 mg/kg i.v.) noticeably enhanced the increase in pulmonary resistance observed during anaphylactic reaction and reduced the protective effect of the H1 antagonists on this parameter and on histamine release. These effects might be explained by an inhibition - at least partial - of the negative feed-back mechanism through which histamine controls its own release, or by a specific action of metiamide in high doses. The transient tachycardia initially observed in anaphylactic shock is partly related to stimulation of cardiac H2 receptors by the histamine released, since it is suppressed by metiamide.

1 Propranolol increased pulmonary airway resistance (PAR) in the conscious guinea-pig, whereas atropine had no effect, suggesting the existence of a continual sympathetic bronchodilator tone. 2 The direct bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were modified by autonomic reflexes: a bronchodilator one, abolished by propranolol, and a cholinergic bronchoconstrictor one, seen with histamine. 3 Pentobarbitone increased PAR, an effect which was reduced by propranolol but which was unaffected by atropine. The bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were potentiated by pentobarbitone. 4 Pentobarbitone therefore appears to inhibit the adrenergic bronchodilator tone and to depress adrenergic reflexes, these being the preponderant autonomic influences in these experiments. 5 Like pentobarbitone, urethane increased PAR in the conscious guinea-pig and potentiated the bronchoconstrictor effects of the three amines. These actions are similarly attributed to a reduction in adrenergic influences.