Sympathomimetic enantiomers and asthma.
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.
Handley
D A
DA
Sepracor Inc., Marlborough, Massachusetts, USA.
McCullough
J R
JR
Crowther
S D
SD
Morley
J
J
D000420:Albuterol / Q000737:chemistry / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001249:Asthma / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D001986:Bronchial Spasm / Q000139:chemically induced / Q000503:physiopathology; D002986:Clinical Trials as Topic; D006801:Humans; D007545:Isoproterenol / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013566:Sympathomimetics / Q000737:chemistry / Q000493:pharmacokinetics*
D018927:Anti-Asthmatic Agents; D013566:Sympathomimetics; D007545:Isoproterenol; D000420:Albuterol