Oliver D W, Dormehl I C, Hugo N
Department of Pharmacology, Potchefstroom University for Christian Higher Education (C.H.E.), Pretoria, Republic of South Africa.
Arzneimittelforschung. 1994 Aug;44(8):925-8.
Changes in cerebral blood flow are implicated to be important in the pathophysiology of migraine. Furthermore, serotonin (5-HT) is known to be the most important substance in the etiology of migraine. Sumatriptan (CAS 103628-46-2), a 5-HTID receptor agonist was recently introduced in the treatment of migraine. In the present study a baboon model was used to investigate the changes in cerebral blood flow due to anaesthesia and pharmacological interventions using 99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) and single photon emission computed tomography (SPECT). The effect of sumatriptan on cerebral blood flow was investigated after 10 min and again after 23 min, with the animal under anaesthesia, i.e. induction with ketamine and maintenance on thiopental. Sumatriptan did not alter the cerebral blood flow during the 10 min procedure. However, sumatriptan reversed the increased cerebral blood flow due to the prolonged anaesthesia (23 min), lowering the cerebral blood flow by more than 20%. No significant changes in the biochemical parameters (blood pressure, heart rate, pO2 and pCO2) were observed. These results also suggest that sumatriptan reverses the increased cerebral blood flow most likely via 5-HTID receptor stimulation.
脑血流量的变化被认为在偏头痛的病理生理学中起着重要作用。此外,血清素(5-羟色胺,5-HT)是已知的偏头痛病因中最重要的物质。舒马曲坦(化学物质登记号103628-46-2),一种5-HTID受体激动剂,最近被用于偏头痛的治疗。在本研究中,使用狒狒模型,采用99mTc标记的六甲丙二胺肟(99mTc-HMPAO)和单光子发射计算机断层扫描(SPECT)来研究麻醉和药物干预引起的脑血流量变化。在动物麻醉状态下(即氯胺酮诱导、硫喷妥钠维持麻醉),分别于10分钟和23分钟后研究舒马曲坦对脑血流量的影响。在10分钟的过程中,舒马曲坦未改变脑血流量。然而,舒马曲坦逆转了因长时间麻醉(23分钟)导致的脑血流量增加,使脑血流量降低了20%以上。未观察到生化参数(血压、心率、pO2和pCO2)有显著变化。这些结果还表明,舒马曲坦最有可能通过刺激5-HTID受体来逆转脑血流量的增加。