[Synthesis of substituted 6-phenylpyrazolo[3,4-d]pyrimidines with potential adenosin-A2A antagonistic activity].

Substituted pyrazolo[3,4-d]pyrimidines were prepared by reaction of methyl- or phenylhydrazine with pyrimidine derivatives containing a methylthio or chlorine substituent as nucleofuge. Using a methylthio-6-imino-1,3-thiazine as starting material instead of a methylthiopyrimidine the conversion with phenylhydrazine could already be achieved under mild conditions thus leading first to the formation of a hydrazinopyrimidine. The affinity of the products against the human adenosine A2A receptor was determined.

Indications about the shape of the universe from the Wilkinson microwave anisotropy probe data.

It is shown that the recent observations of NASA's Explorer mission, "Wilkinson Microwave Anisotropy Probe," hint that our Universe may possess a nontrivial topology. As an example we discuss the Picard space which is stretched out into an infinitely long horn but with finite volume.

Comparative efficacy of azelastine nasal spray and terfenadine in seasonal and perennial rhinitis.

The efficacy and tolerability of intranasal azelastine (0.14 mg/nostril twice daily) and oral terfenadine (60 mg twice daily) were compared under double-blind conditions in two 6-week, multicenter, parallel-group studies, including 167 patients suffering from seasonal and 52 patients suffering from perennial allergic rhinitis. In both studies, patients were symptomatic on entry and showed significant improvement on both treatments within the first 8 d of therapy, showing little further improvement with continued treatment.

Efficacy and tolerability of azelastine nasal spray in patients with allergic rhinitis compared to placebo and budesonide.

The efficacy and safety of a new antiallergic drug, intranasal azelastine (CAS 58581-89-8), in the treatment of seasonal allergic rhinitis was investigated in a 16 patient double-blind comparison with placebo and another 36 patient open comparison with budesonide (CAS 51333-22-3). Efficacy was assessed in terms of 13 signs and symptoms of allergic rhinitis and tolerability on the basis of spontaneously reported adverse events. In the first study, compared to placebo a one week's treatment with azelastine resulted in substantial relief of sneezing (p = 0.

Investigation of long-term efficacy and tolerability of azelastine nasal spray in the treatment of perennial allergic rhinitis.

The long-term efficacy and tolerability of azelastine (CAS 58581-89-8) nasal spray (0.14 mg/nostril b.i.

Intranasal treatment of perennial allergic rhinitis. Comparison of azelastine nasal spray and budesonide nasal aerosol.

The efficacy and tolerability of azelastine (CAS 58581-89-8) nasal spray (0.14 mg/nostril b.i.

Dose related protective effect of azelastine on histamine induced bronchoconstriction in extrinsic asthma.

The effect of single oral doses of the antiallergic agent azelastine hydrochloride (1.1, 2.2 and 4.

[Creatine kinase risk groups in acute myocardial infarct].

The individual valuation of risks in patients with acute myocardial infarction on the basis of a monitoring of the creatine kinase (CK) is made evident as relevant to practice for the basic medical care. Thereby a classification of risk groups on the basis of CKmax (less than or equal to 23; greater than 23 less than or equal to 40; greater than 40 less than or equal to 60; greater than 60 mumol/l.s) is controlled.

The inhibitory actions of azelastine hydrochloride on the early and late bronchoconstrictor responses to inhaled allergen in atopic asthma.

We have examined the effect of azelastine hydrochloride, 8.8 mg, on the early and late responses to inhaled allergen in a group of 12 atopic subjects with asthma. On two separate days, 3 weeks apart, patients were administered either oral azelastine, 8.

Duration of the effect of a single dose of azelastine on histamine-induced bronchoconstriction.

We studied the duration of the protective effect of azelastine against histamine-induced bronchoconstriction in six subjects with asymptomatic asthma. The study was performed in two periods of five consecutive days each. After a histamine inhalation test, we randomly administered either placebo or a single oral dose of 8.

The in vivo potency and selectivity of azelastine as an H1 histamine-receptor antagonist in human airways and skin.

Azelastine is a novel histamine H1 antagonist with putative antileukotriene activity in guinea pigs. With three different doses of oral azelastine, we have performed a dose-response study to determine its protective effect on the airways against histamine-induced bronchoconstriction in 12 patients with mild, atopic asthma. On 4 separate days, patients undertook standardized inhalation-challenge tests with increasing concentrations of histamine (0.

A study of the clinical efficacy of azelastine in patients with extrinsic asthma, and its effect on airway responsiveness.

1. The effect of 4.4 mg azelastine administered orally on airway responsiveness, skin prick testing, daily peak expiratory flow rates and symptoms of asthma was compared with placebo in a 7 week double-blind, parallel group study of 24 patients with extrinsic asthma.

The effect of azelastine on exercise-induced asthma.

In ten young asthmatic subjects, we studied the effect of a single oral dose of 4.4 mg of azelastine hydrochloride on exercise-induced bronchoconstriction during the breathing of cold air. Exercise challenges were performed on two different days before and four hours after azelastine and placebo given in a randomized double-blind crossover fashion.

The effect of repeated oral doses of azelastine hydrochloride on antipyrine half-life in normal volunteers.

Treatment with azelastine 4.4 mg twice daily for 21 days did not produce any change in salivary antipyrine elimination in 8 normal volunteers.

Comparative studies of atropine methonitrate and its combination with reproterol in chronic airway obstruction.

The therapeutic value of 80 micrograms atropine methonitrate delivered per metered aerosol and its combination with 450 micrograms reproterol was investigated in a controlled double-blind cross-over trial in 17 patients with chronic bronchitis and airway obstruction. All patients were atropine responders. According to the parameters of FEV1 and SGaw atropine methonitrate induced a statistically definite and clinically relevant bronchodilation for more than 3 h compared with placebo.

[Bronchospasmolytic effect of reproterol as aerosol (author's transl)].

In an intraindividual double-blind study the effect of 1% (2.5 mg) and 2% (5 mg) reproterol aerosol was investigated in 30 patients with chronic obstructive bronchitis and asthma. Both solutions had a statistically highly significant bronchospasmolytic effect when airways resistance and specific conductance were measured.