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Contractile responses evoked by dihydroergotamine, naratriptan and sumatriptan in the canine isolated coronary artery
Author(s) -
Valentin JP,
Bonnafous R,
John GW
Publication year - 1998
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1998.tb00935.x
Subject(s) - sumatriptan , dihydroergotamine , chemistry , vasodilation , anesthesia , medicine , endocrinology , pharmacology , agonist , migraine , receptor
Summary— Contractile responses evoked by the 5‐HT 1B/D receptor agonists, dihydroergotamine, naratriptan and sumatriptan, were compared in canine isolated coronary artery rings before and after endothelial dysfunction as obtained by inhibition of nitric oxide synthase with Nω‐nitro‐L‐arginine methyl ester (L‐NAME; 10 μM). The three agonists contracted rings in the potency order of dihydroergotamine (geometric mean pD 2 value with 95% confidence limits in parentheses: 6.9 [5.3–7.9] and 7.0 [5.4–7.3] in the absence and presence of nitric oxide synthase (NOS) inhibition [I], respectively) ≥ naratriptan (6.8 [5.7–7.3] and 6.4 [5.7–6.6]) > sumatriptan (4.8 [3.6–5.6] and 5.0 [3.6–5.6]) independently of the presence or absence of L‐NAME. In absence of L‐NAME, efficacy, as assessed by the mean maximal contractile response (Emax), tended to be greater, although not significantly, for sumatriptan and naratriptan compared to dihydroergotamine. L‐NAME per se markedly increased developed tension (43.0 ± 4.6 mN; n = 50) and potentiated maximal responses (0.6 ± 0.2 and 10.7 ± 2.4 mN for dihydroergotamine in the absence and presence of L‐NAME respectively; 1.7 ± 0.6 and 18.7 ± 3.7 mN for naratriptan; 2.5 ± 0.6 and 21.3 ± 3.8 mN for sumatriptan; P < 0.01 in each case). Emax values of sumatriptan and naratriptan were greater than those produced by dihydroergotamine in the presence of L‐NAME but remained lower than the sub‐maximal contractile responses evoked by the thromboxane A 2 analogue, U‐46619 (ie, 32.4 ± 5.2 mN in the absence of L‐NAME; n = 50), or L‐NAME per se. In conclusion, 5‐HT 1B/D receptor agonist efficacies in contracting coronary arteries are relatively low under basal conditions and are potentiated in the presence of a dysfunctional endothelium, whereas agonist potencies remain unaffected.