Research into the correlates of physical activity has focused almost exclusively on physical activity as an omnibus construct. Health Canada and the American College of Sports Medicine, however, advocate physical activity in terms of performing regular endurance, strength, and flexibility activities. The purpose of this study was to investigate the absolute and relative contributions of behavioral, normative, and control beliefs associated with endurance, strength, and flexibility activities within a theory of planned behavior (TPB) structure. Participants were 185 undergraduates who completed measures of the TPB and a 2-week follow-up of endurance, strength, and flexibility behavior. Results using structural equation modeling and Hotelling's t-tests for dependent correlations identified different motivational antecedents for each type of physical activity (p < .05). Endurance behavior was influenced exclusively by behavioral beliefs, flexibility behavior was influenced by normative and control beliefs, and strength behavior was influenced by key behavioral, normative, and control beliefs. The different motivational profiles for each physical activity allude to the importance of tailoring interventions by physical activity type.

Aims To compare the airway potency, systemic activity and therapeutic index of three inhaled corticosteroids that differ in glucocorticoid receptor binding affinity, physicochemical and pharmacokinetic properties. Methods This escalating‐dose, placebo‐controlled, cross‐over study randomised adults with asthma to 1 or 2 treatment periods with ≥25 days washout in‐between. Each treatment period comprised five 7‐day dose escalations (μg/d): fluticasone furoate (FF; 25 → 100 → 200 → 400 → 800), fluticasone propionate (FP; 50 → 200 → 500 → 1000 → 2000), budesonide (BUD; 100 → 400 → 800 → 1600 → 3200) or placebo. Airway hyperresponsiveness to adenosine‐5'‐monophosphate (AMP PC20) was assessed on day 8. Plasma cortisol was assessed on day 1 (predose baseline) and from pre‐PM dose on day 6 to pre‐PM dose day 7 (24‐h weighted mean). Results Fifty‐four subjects were randomised. FF showed greater airway potency than FP and BUD (AMP PC20 dose at which 50% of the maximum effect is achieved [ED50] values: 48.52, 1081.27 and 1467.36 μg/d, respectively). Systemic activity (cortisol suppression) ED50 values were 899.99, 1986.05 and 1927.42 μg/d, respectively. The therapeutic index (ED50 cortisol suppression/ED50 AMP PC20) was wider for FF (18.55) than FP (1.84) and BUD (1.31). FF 100 μg/d and 200 μg/d were both comparable in terms of airway potency with high doses of FP (≥1000 μg twice daily [BID]) and BUD (≥1500 μg/BID). The systemic activity of FF 100 μg/d and 200 μg/d (cortisol suppression: 7.41% and 14.28%, respectively) was comparable with low doses of FP (100 μg/BID and 250 μg/BID) and BUD (100 μg/BID and 200 μg/BID). Conclusion This study provides evidence that FF can provide more protection against airway hyperresponsiveness, with less systemic activity, than FP or BUD. This suggests that all inhaled corticosteroids are not therapeutically similar and may differ in their therapeutic index. (203162; NCT02991859).

It has previously been reported that a 3-(3-(piperazin-1-yl)propyl)indole series of 5-HT1D receptor ligands have pharmacokinetic advantages over the corresponding 3-(3-(piperidin-1-yl)propyl)indole series and that the reduced pKa of the piperazines compared to the piperidines may be one possible explanation for these differences. To investigate this proposal we have developed versatile synthetic strategies for the incorporation of fluorine into these ligands, producing novel series of 4-fluoropiperidines, 3-fluoro-4-aminopiperidines, and both piperazine and piperidine derivatives with one or two fluorines in the propyl linker. Ligands were identified which maintained high affinity and selectivity for the 5-HT1D receptor and showed agonist efficacy in vitro. The incorporation of fluorine was found to significantly reduce the pKa of the compounds, and this reduction of basicity was shown to have a dramatic, beneficial influence on oral absorption, although the effect on oral bioavailability could not always be accurately predicted.

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