The pharmacological profile of tasipimidine, a novel orally active α₂-adrenoceptor agonist developed for situational anxiety and fear in dogs, was studied in various in vitro and in vivo models. In the cell assays, tasipimidine demonstrated binding affinity and full agonism on the human α_2A-adrenoceptors with a pEC50 of 7.57, while agonism on the α_2B-and α_2C-adrenoceptors and the rodent α_2D-adrenoceptor was weaker, resulting in pEC50 values of 6.00, 6.29 and 6.56, respectively. Tasipimidine had a low binding affinity on the human α₁-adrenoceptors. It had no functional effects in the LNCaP cells expressing endogenously the human α_1A-adrenoceptors but was a weak agonist in the Chem-1 cells coexpressing Gα15 protein and α_1A-adrenoceptors. In the recombinant CHO cells, although tasipimidine was a weak partial agonist in the inositol monophosphate accumulation assay, it was a full agonist in the intracellular [Ca²⁺] assay. No functional effects were observed on the human α_1B-adrenoceptor, whereas in the rat α_1A and α_1B-adrenoceptors, tasipimidine was a weak partial agonist. In the rat vas deferens preparations, tasipimidine was a full agonist on the α_2D-adrenoceptor but weak partial agonist on the α₁-adrenoceptor. The receptor profile of tasipimidine indicated few secondary targets, and no functional effects were observed. Sedative effects of tasipimidine were demonstrated in vivo by the reduced acoustic startle reflex in rats with subcutaneous doses and decreased spontaneous locomotor activity in mice with subcutaneous and higher oral doses. It may be concluded that tasipimidine is an orally active and selective α_2A-adrenoceptor agonist.

The pharmacological profile of tasipimidine, a novel orally active α₂-adrenoceptor agonist developed for situational anxiety and fear in dogs, was studied in various in vitro and in vivo models. In the cell assays, tasipimidine demonstrated binding affinity and full agonism on the human α_2A-adrenoceptors with a pEC50 of 7.57, while agonism on the α_2B-and α_2C-adrenoceptors and the rodent α_2D-adrenoceptor was weaker, resulting in pEC50 values of 6.00, 6.29 and 6.56, respectively. Tasipimidine had a low binding affinity on the human α₁-adrenoceptors. It had no functional effects in the LNCaP cells expressing endogenously the human α_1A-adrenoceptors but was a weak agonist in the Chem-1 cells coexpressing Gα15 protein and α_1A-adrenoceptors. In the recombinant CHO cells, although tasipimidine was a weak partial agonist in the inositol monophosphate accumulation assay, it was a full agonist in the intracellular [Ca²⁺] assay. No functional effects were observed on the human α_1B-adrenoceptor, whereas in the rat α_1A and α_1B-adrenoceptors, tasipimidine was a weak partial agonist. In the rat vas deferens preparations, tasipimidine was a full agonist on the α_2D-adrenoceptor but weak partial agonist on the α₁-adrenoceptor. The receptor profile of tasipimidine indicated few secondary targets, and no functional effects were observed. Sedative effects of tasipimidine were demonstrated in vivo by the reduced acoustic startle reflex in rats with subcutaneous doses and decreased spontaneous locomotor activity in mice with subcutaneous and higher oral doses. It may be concluded that tasipimidine is an orally active and selective α_2A-adrenoceptor agonist.

tasipimidine 是一种新型口服活性 α ₂ - 肾上腺素受体激动剂，用于治疗犬的情境焦虑和恐惧，其药理学特征已在各种体外和体内模型中进行了研究。在细胞试验中，tasipimidine 对人 α _2A肾上腺素受体表现出结合亲和力和完全激动作用，pEC50 为 7.57，而对 α _2B和 α _2C肾上腺素受体和啮齿动物 α _2D肾上腺素受体的激动作用较弱，导致 pEC50值分别为 6.00、6.29 和 6.56。Tasipimidine 对人 α ₁ -肾上腺素受体具有低结合亲和力。它在内源性表达人α的LNCaP细胞中没有功能影响_1A-adrenoceptors but was a weak agonist in the Chem-1 cells coexpressing Gα15 protein and α_1A-adrenoceptors. In the recombinant CHO cells, although tasipimidine was a weak partial agonist in the inositol monophosphate accumulation assay, it was a full agonist in the intracellular [Ca²⁺] assay. No functional effects were observed on the human α_1B-adrenoceptor, whereas in the rat α_1A and α_1B-adrenoceptors, tasipimidine was a weak partial agonist. In the rat vas deferens preparations, tasipimidine was a full agonist on the α_2D-adrenoceptor but weak partial agonist on the α₁-肾上腺素受体。tasipimidine 的受体谱表明次要靶点很少，并且没有观察到功能效应。tasipimidine 的镇静作用在体内通过皮下剂量降低大鼠的听觉惊吓反射和皮下和更高口服剂量小鼠的自发运动活动降低来证明。可以得出结论，tasipimidine 是一种具有口服活性和选择性的 α _2A -肾上腺素受体激动剂。

tasipimidine 是一种新型口服活性 α ₂ - 肾上腺素受体激动剂，用于治疗犬的情境焦虑和恐惧，其药理学特征已在各种体外和体内模型中进行了研究。在细胞试验中，tasipimidine 对人 α _2A肾上腺素受体表现出结合亲和力和完全激动作用，pEC50 为 7.57，而对 α _2B和 α _2C肾上腺素受体和啮齿动物 α _2D肾上腺素受体的激动作用较弱，导致 pEC50值分别为 6.00、6.29 和 6.56。Tasipimidine 对人 α ₁ -肾上腺素受体具有低结合亲和力。它在内源性表达人α的LNCaP细胞中没有功能影响_1A - 肾上腺素受体，但在共表达 Gα15 蛋白和 α _1A -肾上腺素受体的 Chem-1 细胞中是弱激动剂。在重组CHO细胞中，虽然tasipimidine在肌醇一磷酸积累试验中是弱的部分激动剂，但在细胞内[Ca ²⁺ ]试验中是完全激动剂。_{对人 α 1B} -肾上腺素受体没有观察到功能影响，而在大鼠 α _1A和 α _1B -肾上腺素受体中，tasipimidine 是一种弱部分激动剂。在大鼠输精管制剂中，tasipimidine 是 α _{2D肾上腺素受体的完全激动剂，但对 α 1}是弱部分激动剂。-肾上腺素受体。tasipimidine 的受体谱表明次要靶点很少，并且没有观察到功能效应。tasipimidine 的镇静作用在体内通过皮下剂量降低大鼠的听觉惊吓反射和皮下和更高口服剂量小鼠的自发运动活动降低来证明。可以得出结论，tasipimidine 是一种具有口服活性和选择性的 α _2A -肾上腺素受体激动剂。