Tachyphylaxis asthma

Detailed accounts have been published of the synthesis, structure activity relationships and pharmacology of a series of bronchospasmolytic 0-phenylethylaminoalkylxanthines, of which (13) (reproterol, D 1959) was selected for clinical trial. 13 is a /3-2 agonist with minimal CNS or CV side effects and is clinically effective against bronchial asthma and chronic bronchitis (orally or by inhalation) with no tachyphylaxis after 4... 

Continued stimulation of cells with agonists generally results in a state of desensitization (also referred to as adaptation, refractoriness, or down-regulation) such that the effect that follows continued or subsequent exposure to the same concentration of drug is diminished. This phenomenon, called tachyphylaxis, occurs rapidly and is important therapeutically an example is attenuated response to the repeated use of receptor agonists as bronchodUators for the treatment of asthma (see Chapters 10 and 27). 

Another example of marked B-adrenoreceptor potency enhancement by N-substltution is illustrated by fenoterol (60a). which is strikingly more potent than its N-tert-butyl counterpart, ter-butallne (6. Fenoterol is a clinically effective bronchodilator by either oral or aerosol administration however, some cardiac stimulation and tremors are noted (136, 137). Cat soleus muscle, bronchial and heart rate experiments indicate selective B2 adrenoreceptor potency for 60b (138). Another resorcinol, one of a series of xanthine derivatives, is reproterol (60c). Repro-terol is clinically effective in bronchial asthma it causes minimum CNS and cardiovascular side effects upon administration orally or by inhalation, and tachyphylaxis is not observed (139). 

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