Antitussive activity of sigma-1 receptor agonists in the guinea-pig

1. Current antitussive medications have limited efficacy and often contain the opiate-like agent dextromethorphan (DEX). The mechanism whereby DEX inhibits cough is ill defined. DEX displays affinity at both NMDA and sigma receptors, suggesting that the antitussive activity may involve central or peripheral activity at either of these receptors. This study examined and compared the antitussive activity of DEX and various putative sigma receptor agonists in the guinea-pig citric-acid cough model. 2. Intraperitoneal (i.p.) administration of DEX (30 mg kg(−1)) and the sigma-1 agonists SKF-10,047 (1–5 mg kg(−1)), Pre-084 (5 mg kg(−1)), and carbetapentane (1–5 mg kg(−1)) inhibited citric-acid-induced cough in guinea-pigs. Intraperitoneal administration of a sigma-1 antagonist, BD 1047 (1–5 mg kg(−1)), reversed the inhibition of cough elicited by SKF-10,047. In addition, two structurally dissimilar sigma agonists SKF-10,047 (1 mg ml(−1)) and Pre-084 (1 mg ml(−1)) inhibited cough when administered by aerosol. 3. Aerosolized BD 1047 (1 mg ml(−1), 30 min) prevented the antitussive action of SKF-10,047 (5 mg kg(−1)) or DEX (30 mg kg(−1)) given by i.p. administration and, likewise, i.p. administration of BD 1047 (5 mg kg(−1)) prevented the antitussive action of SKF-10,047 given by aerosol (1 mg ml(−1)). 4. These results therefore support the argument that antitussive effects of DEX may be mediated via sigma receptors, since both systemic and aerosol administration of sigma-1 receptor agonists inhibit citric-acid-induced cough in guinea-pigs. While significant systemic exposure is possible with aerosol administration, the very low doses administered (estimated <0.3 mg kg(−1)) suggest that there may be a peripheral component to the antitussive effect

Exercise Professionals with Advanced Clinical Training Should be Afforded Greater Responsibility in Pre-Participation Exercise Screening: A New Collaborative Model between Exercise Professionals and Physicians

© 2018 The Author(s) Regular exercise improves health but can also induce adverse responses. Although such episodes are rare, many guidelines for pre-participation exercise screening have historically had a low threshold for recommending medical clearance prior to the commencement of exercise, placing the responsibility for decision making about exercise participation on physicians. The ‘clearance to exercise’ model still occurs widely in practice, but creates cost burdens and barriers to the uptake of exercise. Moreover, many physicians are not provided the training, nor time in a standard consultation, to be able to effectively perform this role. We present a model for pre-participation exercise screening and the initial assessment of clients wishing to commence an exercise programme. It is designed to guide professional practice for the referral, assessment and prescription of exercise for people across the health spectrum, from individuals who are apparently healthy, through to clients with pre-existing or occult chronic conditions. The model removes the request that physicians provide a ‘clearance’ for patients to engage in exercise programmes. Instead the role of physicians is identified as providing relevant clinical guidance to suitably qualified exercise professionals to allow them to use their knowledge, skills and expertise in exercise prescription to assess and manage any risks related to the prescription and delivery of appropriate exercise programmes. It is anticipated that removing unjustified barriers to exercise participation, such as mandated medical review, will improve the uptake of exercise by the unacceptably high proportion of the population who do not undertake sufficient physical activity for health benefit