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- Krarup, Anne L., et al.
(author)
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Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain.
- 2011
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In: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 33:10, s. 1113-22
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Journal article (peer-reviewed)abstract
- Background Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor ‘transient receptor potential vanilloid 1’(TRPV1) are a potential drug class for GERD treatment. Aim To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain. Methods Twenty-two healthy men (20–31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. Data analysis: intention-to-treat. Results A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10–38%] and 28%, respectively (CI: 14–43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1–3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0–5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported ‘feeling cold’ and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4 ± 0.3 °C and 0.7 ± 0.3 °C, respectively, P < 0.05). Conclusions AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD (ClinicalTrials.gov identifier: NCT00711048).
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- Aidas, Kestutis, et al.
(author)
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The Dalton quantum chemistry program system
- 2014
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In: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Journal article (peer-reviewed)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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