Handley D A, McCullough J R, Crowther S D, Morley J
Sepracor Inc., Marlborough, Massachusetts, USA.
Chirality. 1998;10(3):262-72. doi: 10.1002/(SICI)1520-636X(1998)10:3<262::AID-CHIR9>3.0.CO;2-B.
Airways of asthma patients can become hyperresponsive to airway spasmogens following regular use of isoprenaline or beta 2-selective sympathomimetics. Hyper-reactivity that results from acute exposure of animals to these drugs is pre-empted by vagal section (a procedure which does not influence spasmolytic efficacy of sympathomimetics), is not diminished by antagonism of beta 2-adrenoceptors and is not associated with loss of responsivity of beta 2-adrenoceptors in the airways. Since activation, modulation, or blockade of beta 2-adrenoceptors does not determine this form of hyperreactivity, the possibility that distomers may induce hyperreactivity must be considered. Ocular and vascular responses to distomers of sympathomimetics have long been recognised and, more recently, comparable observations have been made for the airways. Thus, reactivity of guinea-pig airways to spasmogens was increased following exposure to S-isoprenaline, S-salbutamol, or S-terbutaline and exposure to S-isoprenaline or S-salbutamol can intensify symptoms in asthmatics. Regular exposure to the racemate, especially during or following an allergic reaction, predisposes to expression of hyper-reactivity, which is nullified, acutely, by the eutomer. These observations imply that biological effects of sympathomimetic distomers may contribute to morbidity and mortality in asthma patients.
哮喘患者的气道在长期使用异丙肾上腺素或β2选择性拟交感神经药后，可能会对气道痉挛原产生高反应性。动物急性接触这些药物所导致的高反应性，可通过迷走神经切断术（此手术不影响拟交感神经药的解痉效力）预先消除，不会因β2肾上腺素能受体的拮抗作用而减弱，也与气道中β2肾上腺素能受体反应性的丧失无关。由于β2肾上腺素能受体的激活、调节或阻断并不能决定这种形式的高反应性，所以必须考虑对映体可能诱发高反应性的可能性。拟交感神经药对映体的眼部和血管反应早已为人所知，最近在气道方面也有类似的观察结果。因此，豚鼠气道在接触S-异丙肾上腺素、S-沙丁胺醇或S-特布他林后，对痉挛原的反应性增强，且接触S-异丙肾上腺素或S-沙丁胺醇会加重哮喘患者的症状。长期接触外消旋体，尤其是在过敏反应期间或之后，容易引发高反应性的表现，而优映体可急性消除这种高反应性。这些观察结果表明，拟交感神经药对映体的生物学效应可能导致哮喘患者的发病和死亡。
