The haemodynamic effect of the 5HT1 agonist BMS-180048: a class effect of triptans?
OBJECTIVE
To investigate the effects of an intravenous infusion of BMS-180048, a novel 5HT1-like agonist, on the systemic, pulmonary and coronary circulations in patients undergoing diagnostic cardiac catheterisation.


METHODS
Ten patients (mean age 55 years (range 41-65)) were studied during diagnostic cardiac catheterisation. The haemodynamic response to an intravenous (i.v.) infusion for 30 min of BMS-180048 (0.56 mg kg(-1) h(-1) for 10 min and 0.39 mg kg(-1) h(-1) for 20 min) was assessed via a 7F Swan Ganz catheter and thermodilution cardiac output system. Quantitative coronary angiography was performed at 10 min intervals.


RESULTS
BMS-180048 caused a significant increase in systemic arterial systolic blood pressure (rise of 32.5 mmHg, 95% CI 24,44.5) P=0.009), pulmonary artery systolic (12.2 mmHg, 95% CI 6.8,18.5; P=0.009) and diastolic pressures (8.5 mmHg, 95% CI 5.0,13.8; P=0.009), right atrial pressure (4 mmHg, 95% CI 1.5,5.2; P=0.013) and pulmonary capillary wedge pressure (9.5 mmHg 95% CI 5.2,14.0; P=0.09). There was no significant change in cardiac output (0.1 l min(-1), 95% CI -0.17,0.57, P>0.05). Mean coronary artery diameter in the proximal coronary segments decreased by 0.73 mm (95% CI -1.22,-0.15; P=0.03) at 35 min. The corresponding reduction in middle segments was 0.26 mm (95% CI -0.395,-0.08; P=0.02). There was a non-significant trend to constriction in the most distal segments of 0.28 mm (95% CI -0.68,0.015); P=0.06). One patient experienced chest pain with ECG changes suggestive of ischaemia.


CONCLUSIONS
BMS-180048 displayed a cardiovascular profile similar to that previously reported for sumatriptan. These changes appear to reflect a class effect of these agents.
Swan
L
L
Department of Medicine and Therapeutics, University of Glasgow, UK.
Hood
S
S
Birnie
D H
DH
Muir
D F
DF
McCann
G P
GP
Hillis
W S
WS
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000187:drug effects*; D015203:Reproducibility of Results; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology*; D014363:Tryptamines; D014661:Vasoconstriction / Q000187:drug effects
D007211:Indoles; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D014363:Tryptamines; C103231:avitriptan