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Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs. Opioids are the mainstay for the treatment of moderate to severe pain. However, opioid pain medications also cause detrimental side effects, thus highlighting the need of innovative and safer analgesics. Opioids mediate their actions via the activation of opioid receptors, with the mu-opioid receptor as the primary target for analgesia, but also for side effects. One long-standing focus of drug discovery is the pursuit for new opioids exhibiting a favorable dissociation between analgesia and adverse effects. In this study, we describe the and pharmacological profiles of the 14- -phenylpropyl substituted analog of the mu-opioid agonist 14- -methyloxymorphone (14-OMO). The consequence of the substitution of the 14- -methyl in 14-OMO with a 14- -phenylpropyl group on binding and functional activity, and behavioral properties (nociception and gastrointestinal motility) was investigated. In binding studies, 14- -phenylpropyloxymorphone (POMO) displayed very high affinity at mu-, delta-, and kappa-opioid receptors ( values in nM, mu:delta:kappa = 0.073:0.13:0.30) in rodent brain membranes, with complete loss of mu-receptor selectivity compared to 14-OMO. In guinea-pig ileum and mouse vas deferens bioassays, POMO was a highly efficacious and full agonist, being more potent than 14-OMO. In the [ S]GTPγS binding assays with membranes from CHO cells expressing human opioid receptors, POMO was a potent mu/delta-receptor full agonist and a kappa-receptor partial agonist. , POMO was highly effective in acute thermal nociception (hot-plate test, AD = 0.7 nmol/kg) in mice after subcutaneous administration, with over 70- and 9000-fold increased potency than 14-OMO and morphine, respectively. POMO-induced antinociception is mediated through the activation of the mu-opioid receptor, and it does not involve delta- and kappa-opioid receptors. In the charcoal test, POMO produced fourfold less inhibition of the gastrointestinal transit than 14-OMO and morphine. In summary, POMO emerges as a new potent mixed mu/delta/kappa-opioid receptor agonist with reduced liability to cause constipation at antinociceptive doses.

This book explores contemporary club and dance cultures as a manifestation of aesthetic and prosthetic forms of life. Rief addresses the questions of how practices of clubbing help cultivate particular forms of reflexivity and modes of experience, and how these shape new devices for reconfiguring the boundaries around youth cultural and other social identities. She contributes empirical analyses of how such forms of experience are mediated by the particular structures of night-clubbing economies, the organizational regulation and the local organization of experience in club spaces, the media discourses and imageries, the technologies intervening into the sense system of the body (e.g. music, visuals, drugs) and the academic discourses on dance culture. Although the book draws from local club scenes in London and elsewhere in the UK, it also reflects on similarities and differences between nightclubbing cultures across geographical contexts. 1. Introduction 2. Urban Renewal and Night Life Governance: London and Istanbul 3. Club Cultural Production and the Night-time Economy Market in the UK 4. Sensing and Meaning the Body: The Local Organization of Clubbing Practices 5. Thresholds of Reality: Clubbing, Drugs and Agency 6. Identity Projects and Spectacular Selves 7. Between Style and Desire: Sexual Scenarios in Clubbing Magazines 8. Allegorical Anarchy, Symbolic Hierarchy: Sexual Boundaries in Two London Dance Clubs 9. Conclusion. Appendix. Silvia Rief is a Lecturer in Sociology at the University of Innsbruck.

This thesis investigates experiences of contemporary club and dance cultures in the context of postmodern aestheticisation. Its object of study is the phantasmatic and discursive complex of otherness, transgression and freedom in which contemporary British club and dance cultures are embedded. It argues that clubbing experiences are fabricated through this complex of otherness, which articulates a politics of experience. This refers to contexts that structure experiences of dance cultures. In this respect, the thesis considers the contexts of class, gender and sexuality, structures of the production and consumption of clubbing, the institutional regulation and ordering of club spaces and media discourses and imagery. In analysing socially contextualised meanings of this otherness it examines how these became relevant for the construction of identity. The theoretical agenda of the thesis is to explore aestheticisation as a condition for and as a form of identity construction. This engages with changing modes of reflexivity in the construction of reality and reformulates the issues of style, identity and authenticity. The empirical analysis focuses on modes of reflexivity in constructing realities of sexuality, body and self. Research of this study was carried out in London. The qualitative research design comprised narrative interviewing and ethnographic participation in clubs in central London. A criterion for sampling and for the selection of clubs and interviewees was the dimension of sexuality and the sexual differentiation and codification of club spaces. The interview sample consists of twenty-three interviews with people of mixed genders, sexualities and cultural, national backgrounds.

Back in 1995, Franco Bianchini spoke of the ‘relative underdevelopment of urban night-life in Britain’ compared to other European cities (1995: 123). According to Bianchini, the development of night-life culture was inhibited by the monofunctional British town centres dominated by shops, offi ces and physical structures not particularly conducive to walking the city; by poor public transport provision at night; by the temporal constraints of the licensing hours and a leisure lifestyle that was predominantly home-based (ibid.). More than a decade later the landscape of night life in many British town and city centres hardly matches this dire picture of the past.

Popular and academic representations of clubbing are strongly infused with images of ‘otherness’. The dance club is often regarded as an atmosphere of ecstatic feelings, collective bliss and rapture, and as an ‘other-worldly environment’ (Thornton 1995: 21), where the structures of everyday life are temporarily suspended through thresholds that separate the visitors from daily routines, education, work and family commitments; where social identities are undone and new identifi cations and roles are taken up and played with; where social boundaries between groups dissolve and where participants act out transgressive, carnivalesque bodies. In popular discourses such as magazines, fanzines or websites, clubbing appears as an icon of pleasure and fun. Images of liminality and transgression shape a morality of pleasure and the justifi catory discourse that underpins cultures of clubbing. These images of liminality are ‘built in to the promotion of night-time products’ (Talbot 2007: 19) and frames visitors’ expectations of, and scripts for, a ‘good’ night out.