Key Learning Outcomes for Clinical Pharmacology and Therapeutics Education in Europe: A Modified Delphi Study.

Harmonizing clinical pharmacology and therapeutics (CPT) education in Europe is necessary to ensure that the prescribing competency of future doctors is of a uniform high standard. As there are currently no uniform requirements, our aim was to achieve consensus on key learning outcomes for undergraduate CPT education in Europe. We used a modified Delphi method consisting of three questionnaire rounds and a panel meeting. A total of 129 experts from 27 European countries were asked to rate 307 learning outcomes. In all, 92 experts (71%) completed all three questionnaire rounds, and 33 experts (26%) attended the meeting. 232 learning outcomes from the original list, 15 newly suggested and 5 rephrased outcomes were included. These 252 learning outcomes should be included in undergraduate CPT curricula to ensure that European graduates are able to prescribe safely and effectively. We provide a blueprint of a European core curriculum describing when and how the learning outcomes might be acquired

Synthesis and Pharmacological Activities of 6-Glycine Substituted 14-Phenylpropoxymorphinans, a Novel Class of Opioids with High Opioid Receptor Affinities and Antinociceptive Potencies

The synthesis and the effect of a combination of 6-glycine and 14-phenylpropoxy substitutions in <i>N</i>-methyl- and <i>N</i>-cycloproplymethylmorphinans on biological activities are described. Binding studies revealed that all new 14-phenylpropoxymorphinans (<b>11</b>−<b>18</b>) displayed high affinity to opioid receptors. Replacement of the 14-methoxy group with a phenylpropoxy group led to an enhancement in affinity to all three opioid receptor types, with most pronounced increases in δ and κ activities, hence resulting in a loss of μ receptor selectivity. All compounds (<b>11</b>−<b>18</b>) showed potent and long-lasting antinociceptive effects in the tail-flick test in rats after subcutaneous administration. For the <i>N</i>-methyl derivatives <b>13</b> and <b>14</b>, analgesic potencies were in the range of their 14-methoxy analogues <b>9</b> and <b>10</b>, respectively. Even derivatives <b>15</b>−<b>18</b> with an <i>N</i>-cyclopropylmethyl substituent acted as potent antinociceptive agents, being several fold more potent than morphine. Subcutaneous administration of compounds <b>13</b> and <b>14</b> produced significant and prolonged antinociceptive effects mediated through peripheral opioid mechanisms in carrageenan-induced inflammatory hyperalgesia in rats