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Non-invasive assessment of selective 5-HT(1B/1D)-receptor agonist-induced peripheral vascular effects in humans:
F H Vanmolkot1, J N de Hoon, P Barrington
1Center for Clinical Pharmacology, University Hospital Gasthuisberg, K.U.Leuven, Herestraat 49, 3000 Leuven, Belgium.
Objective:
To compare the sensitivity of three non-invasive techniques for detecting serotonin (5-HT)(1B/1D)-receptor agonist-induced peripheral vascular effects in humans: the measurement of (1) systolic (SBP) and diastolic (DBP) blood pressures, (2) dorsal hand vein (DHV) diameter and (3) toe-arm systolic blood pressure gradient (DeltaSBP(toe-arm)).
Methods:
A double-blind, placebo-controlled, three-way, cross-over study was performed in 12 healthy male volunteers. According to a randomly assigned allocation schedule, subjects were administered sumatriptan 3 mg, sumatriptan 6 mg or placebo subcutaneously. Measurements were performed at baseline, every 5 min for 30 min and at 40 min and 60 min after drug administration. SBP and DBP were recorded using a semi-automated oscillometric device. DHV diameter was measured using a linear variable differential transformer. DeltaSBP(toe-arm) was calculated after measuring toe and arm SBP with a strain-gauge technique. Sensitivity was evaluated with responsiveness statistics.
Results:
Based on weighted mean and compared with placebo, sumatriptan 3 mg and 6 mg increased SBP by 3.3 mmHg ( P=0.023) and 6.4 mmHg ( P<0.001) and DBP by 5.0 mmHg ( P=0.006) and 7.5 mmHg ( P<0.001), respectively. Sumatriptan 3 mg and 6 mg decreased DHV diameter by 36% ( P=0.015) and 40% ( P=0.005), respectively. DeltaSBP(toe-arm) did not change. Peak changes were observed within 10-15 min after drug administration. The rank order of responsiveness was: BP > DHV diameter > DeltaSBP(toe-arm.)
Conclusions:
Clinically relevant doses of subcutaneous sumatriptan increased blood pressure and decreased DHV diameter without affecting DeltaSBP(toe-arm). The increase in blood pressure appeared to be dose dependent. Compared with DHV diameter and DeltaSBP(toe-arm), blood pressure measurement appeared to be the most sensitive technique for detecting selective 5-HT(1B/1D)-receptor agonist-induced peripheral vascular effects in humans.