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Journal of Neuroimmune Pharmacology -     

Sensitization to apomorphine in pigeons is due to conditioning, subject to generalization but resistant to extinction

Apomorphine (Apo) administration induces a persistent bout of pecking in pigeons and other birds. Repeated injections of Apo in pigeons lead to sensitization, i.e. the pecking response to a particular dose increases up to a dose-dependent asymptotic level. It is also known that Apo-induced pecking can be classically conditioned to the cage environment where the animals experience the effect of the drug. Here we address the question of whether, and to what extent, the sensitization effect arises as a consequence of a conditioning or of a pharmacological process. An extinction experiment demonstrated that an extinction procedure supposed to be effective in inhibiting the conditioned pecking response was not effective in suppressing the sensitization to Apo, thus casting provisional doubt on the conditioning hypothesis. However, a conditioning experiment demonstrated that the sensitization effect undoubtedly involved an important component of conditioning to an experimental cage environment, but also suggested that there was an additional component possibly not due to learning. A generalization experiment, however, showed that this second component was very probably due to a stimulus generalization effect deriving from conditioning to the home cage, suggesting that learning can account for most, if not all, of the increase in Apo-induced pecking and that an exclusively pharmacological sensitization process plays, at best, a minor role. The apparent contrast between the results of the first experiment, indicating that the sensitization is not affected by inhibitory conditioning, and the results of the last two experiments, suggesting that the sensitization is due to excitatory conditioning, can be resolved by assuming that Apo induces a drug-state-dependent conditioning. These results are related to findings and arguments concerning the sensitization to psychostimulant drugs in mammals.     

Assessing Similarity to Existing Drugs to Decide Whether to Continue Drug Development

Developing a drug requires large investments, over many years, with dramatic increases in development costs at later stages. Thus, one wants to make a No Go decision on a compound early, unless evidence continues to suggest that the project will ultimately be successful, so that resources can be focused on the most promising compounds to benefit patients. Instead of predicting the probability of success of a Phase III study, our approach to this decision uses the Phase II study results to assess similarity of the novel compound to existing drugs that are classified by different decision categories, such as a clear Go decision (e.g., a clearly effective drug), a (unfortunately common) Not Sure decision (e.g., a potentially useful but not outstanding drug), and a clear No Go decision (e.g., a clearly not effective drug). We describe how this modeling can be done using both individual and binary endpoints and how results can be combined for several different endpoints. Potential extensions of the method are also discussed.     

Ways to increase adherence to allergen immunotherapy

Adherence to allergen immunotherapy (AIT) is crucial for its efficacy. Subcutaneous AIT requires monthly visits (or more extended in the case of venom immunotherapy), while sublingual AIT is performed with a daily intake of allergen drops. Non-adherence to an AIT schedule and premature discontinuation are common problems. Various studies have shown controversial results on the rate of AIT adherence. The aim of this review is to describe the problem of non-adherence and to offer some evidence-based advice to allergologists on how to increase it. Better patient education at the beginning of treatment, sharing with patients the decision on which type of immunotherapy to select and showing sincere interest in their treatment concerns are some tips that can help to increase adherence. A well organized allergologist time schedule not only increases safety but also offers the possibility of close follow-up and an increase in patient loyalty.     

如何对供应商进行质量审计

质量是产品的生命。产品质量不仅要在企业生产过程中得到控制，还应在供应商的原料生产过程中得到控制，这是“上游质量控制”的体现。一个好的制药企业应该对供应商的审计给予足够的重视，审计工作做得好，由原材料供应和原材料质量造成的产品质量问题就可以最大程度地减少，而供应商也能充分了解采购企业的要求并严格进行生产管理，使自己成为采购企业的稳定供应商。因此，供应商质量审计对两者来说是“双赢”的。