The production of ozone-depleting chlorofluorocarbons (CFCs) was discontinued on 1 January 1996 for all uses deemed non-essential under the Montreal Protocol. However, the use of CFCs as propellants in pressurized metered dose inhalers (pMDIs) was classed as essential, providing an exemption from the agreement. Following extensive research, the hydrofluoroalkanes (HFA) 134a and 227 were identified as the only suitable replacements for CFC propellants in pMDIs. The drug delivery of pMDIs formulated with HFA 134a as a propellant and containing either salbutamol (100 microg per actuation) or fluticasone propionate (125 and 250 microg per actuation) have been assessed for dose uniformity and particle size distribution. All of the HFA 134a pMDIs delivered doses throughout the life of the canisters that were reproducible and within specified regulatory requirements. Each of the products provided an emitted dose which was within +/- 25% of the mean value indicating accurate and consistent dosing (93, 112 and 221 microg per metered dose for the salbutamol 100 microg and fluticasone propionate 125 and 250 microg HFA 134a pMDIs, respectively). These findings were unaffected by changing the storage orientation of the pMDI or by using the device in a manner designed to simulate typical patient use. The particle size distributions of HFA 134a pMDI doses did not differ significantly from those of the corresponding CFC pMDIs. As a result of the similar pharmaceutical performance, it is unnecessary to change the label claim dose of active drug when making the transition from a CFC to an HFA 134a pMDI for salbutamol (Ventolin) and fluticasone propionate (Flixotide). A seamless transition to non-CFC pMDIs will help to maintain the confidence of patients and healthcare professionals in asthma therapy.

Serotonin and dopamine play an important role in the aetiology of schizophrenia. Combination of the structural scaffolds of both neurotransmitters in a single molecule lead to aromatic [d,g]-bisannelated azecine derivatives, which have been shown to be nanomolar to subnanomolar dopamine D1-D5 receptor antagonists with a preference for the D1 family. In this work the potential antipsychotic activity of some azecine derivatives was predicted by their dopamine receptor affinities obtained in vitro from radioligand binding experiments and conclusively confirmed in vivo (rats) by applying a conditioned avoidance model. Furthermore, the compounds were tested in vivo for the development of catalepsy, which is a predictive parameter for extra-pyramidal side-effects caused by many antipsychotics. The investigated azecines displayed low cytotoxicity, and the affinities for human dopamine D1-D5 and serotonin 5-HT2 A receptors were in a nanomolar range. In vivo, their antipsychotic activities in the rat model were comparable with those of haloperidol and risperidone, but revealed a 2-5 times better therapeutic range with regard to catalepsy. Preliminary tests for oral bioavailability also revealed promising results for this new class of potential antipsychotic compounds. In conclusion, our in vivo experiments show that aromatic [d,g]-annelated azecines represent a novel and advantageous class of potential atypical neuroleptics.

Objective To analyze the effect of adjuvant oral application of honey for treating postoperative pain after tonsillectomy. Design Single centre prospective cohort study. Setting Two cohorts of patients after tonsillectomy. Participants 56 patients treated with honey 8 times per day (honey group), 18 patients treated without honey (control group); baseline analgesia were non-steroidal anti-inflammatory drugs (NSAID) or coxibs; opioids were used as pro re nata (PRN) medication; mean age 34.4 ± 13.4 years; 36% women. Main outcome measures On first to fifth postoperative day, patients rated their pain using the validated questionnaire of the German-wide project Quality Improvement in Postoperative Pain Treatment (QUIPS) including a numeric rating scale (NRS, 0-10) for determination of patient's pain. QUIPS allows standardized assessment of patients' characteristics andpain-associated patientreported outcomes (PROs). The influence of preoperative and postoperative parameters on patients' postoperative pain were estimated by univariate and multivariate statistical analysis.

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