Cerebral blood flow effects of sumatriptan in drug combinations in the baboon model.
Sumatriptan (CAS 103628-46-2, Imigran) has established itself as an important therapeutic agent in the treatment of migraine. Although considerable understanding of, in particular, the vascular pathophysiology of migraine has been gained during the past decade, the pathophysiology and mediators involved in the pain experience during migraine ar during migraine are not yet fully explained. The mechanisms behind the pharmacological effects of sumatriptan are still only partially understood. In the present study the effects of sumatriptan on drug induced cerebral blood flow increases in the baboon model were investigated using 99mTc-HMPAO (hexamethylpropylene amine oxime) and SPECT (single photon emission computed tomography). Sumatriptan selectively reduced drug induced cerebral blood flow increases. The effects of halothane anaesthesia and acetazolamide on cerebral blood flow were not reversed by sumatriptan, while the effect of nimodipine was attenuated by 47% (to the level of cerebral blood flow below the normal flow baseline). These results support multiple mechanisms for sumatriptan involving vascular neurotransmission and neurogenic inflammatory responses via serotonin receptor stimulation and Ca2+ mobilization. Drug-drug interactions are further implicated through this study.
D000086:Acetazolamide / Q000494:pharmacology; D000758:Anesthesia; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004338:Drug Combinations; D004347:Drug Interactions; D006221:Halothane / Q000494:pharmacology; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D010215:Papio; D018170:Sumatriptan / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000777:Anesthetics; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D014662:Vasoconstrictor Agents; D009553:Nimodipine; D018170:Sumatriptan; D000086:Acetazolamide; D002118:Calcium; D006221:Halothane