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Paradigms for Preclinical Investigations of Female Sexual Function and Dysfunction (HSDD and FSAD)

K. Allers,B. Sommer

Published 2011 in Unknown venue

ABSTRACT

A prerequisite for successful discovery of treatment options for female sexual dysfunction is a deeper understanding of sexual function per se, e.g. which physiological systems are involved, and what goes wrong in a dysfunctional state.. The availability of animal models, which capture the physiological underpinnings of a disorder and have been shown to respond to existing clinical treatments are a major success factor in this endeavor. For example, the translational ability of penile erection models are extremely good, since they have high predictive value for drugs used to treat erectile dysfunction. Predictive validity of models of female sexual dysfunction is less well established. However, results from recent efforts to back-translate effects from drugs that have shown efficacy in clinical trials into laboratory animals provide promising starting points for a better disease understanding and model validation. This chapter will briefly outline those models that have potential in helping understand female sexual function and dysfunction, followed by three examples (flibanserin, bremolantide, apomorphine) of how clinically efficacious compounds contributed to elucidate the physiology and pharmacology underlying both the natural and pathological states (Bechara et al. 2004; Caruso et al. 2004b; Clayton et al. 2010; Safarinejad 2008) of arousal and desire disorders, the major indications in terms of prevalence (Johannes et al. 2009). Modeling a complex human behavior in the laboratory imparts many challenges. Only a few fundamental issues faced in the laboratory are similar in the clinic – ie. the necessity to define a ‘normal’ range of responses for a given function before attempting to assess a dysfunctional range. In the clinic, questionnaire based tools have been developed, that can define ‘healthy’ and ‘dysfunctional’ states of sexual behavior within human populations. Furthermore, the two behavioral domains ‘desire’ and ‘arousal’ become distinguishable when dysfunction is present (DeRogatis et al. 2011). This can principally be achieved in the lab too, since each species has a clear set of behaviors used to solicit sexual contact. Although it is not always easy to separate desire from arousal in rodents as these two components of the sexual response are temporally connected in a natural setting, they can be isolated and studied as distinct physiological pathways. However, in order to have translational relevance, such laboratory studies must address measures aligned with those used clinically. With this request a number of issues arise that are unique to working with

PUBLICATION RECORD

  • Publication year

    2011

  • Venue

    Unknown venue

  • Publication date

    2011-12-22

  • Fields of study

    Medicine, Psychology

  • Identifiers
    DOI 10.5772/26773
  • External record

    Open on Semantic Scholar

  • Source metadata

    Semantic Scholar

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