Hibert M, Middlemiss D N
Neuropharmacology. 1986 Jan;25(1):1-4. doi: 10.1016/0028-3908(86)90050-x.
The enantiomers of the 5-HT autoreceptor antagonist methiothepin have been prepared and their activity as antagonists of the 5-HT autoreceptor and at the 5-HT recognition sites present in the frontal cortex of the rat have been evaluated. At the 5-HT autoreceptor, the order of potency as antagonists of 5-HT was (+)methiothepin (apparent pA2 5.95) less than (+/-)methiothepin (apparent pA2 6.62) less than or equal to (-)methiothepin (apparent pA2 6.81). At the 5-HT2 recognition site, the isomeric forms of methiothepin were potent (pIC50 approximately 8.2) and equiactive. At the subtypes of the 5-HT1 recognition sites, similar concentrations to those blocking the autoreceptor were effective and (+)methiothepin was less active than (-)methiothepin. It is concluded that the chiral association of methiothepin with the 5-HT autoreceptor provides further evidence for a pharmacological similarity between this receptor and the 5-HT1B subtype of the 5-HT1 recognition site.
已制备了5-羟色胺（5-HT）自身受体拮抗剂甲硫噻吨的对映体，并评估了它们作为5-HT自身受体拮抗剂以及在大鼠额叶皮质中存在的5-HT识别位点的活性。在5-HT自身受体上，作为5-HT拮抗剂的效力顺序为：（+）甲硫噻吨（表观pA2 5.95）小于（+/-）甲硫噻吨（表观pA2 6.62）小于或等于（-）甲硫噻吨（表观pA2 6.81）。在5-HT2识别位点，甲硫噻吨的异构体形式效力很强（pIC50约为8.2）且活性相当。在5-HT1识别位点的亚型上，与阻断自身受体的浓度相似的浓度有效，且（+）甲硫噻吨的活性低于（-）甲硫噻吨。结论是，甲硫噻吨与5-HT自身受体的手性结合为该受体与5-HT1识别位点的5-HT1B亚型之间药理相似性提供了进一步证据。
