A series of single dose studies has been undertaken after intravenous, subcutaneous and oral administration to healthy volunteers to determine safety, tolerability and pharmacokinetics of GR43175, a novel 5-HT 1-like receptor agonist. GR43175 proved to be well tolerated using all routes of administration. Minor side effects were reported including scalp tingling, sensations of bodily warmth, lightheadedness and heavyheadedness. In addition, short-lasting vasopressor effects were encountered, although no drug-related changes were seen in heart rate and ECG or in laboratory safety screens. The drug was rapidly absorbed after oral dosing and had a mean absolute bioavailability of 14% due at least in part to first-pass metabolism. Plasma concentrations in healthy volunteers fell within the range for producing relief of headaches in migraine patients. GR43175 had a high mean plasma clearance (1313 ml/min), the majority of which was due to non-renal clearance and a large volume of distribution (2351). The mean half-lives were 1.7 h and 2.3 h after intravenous and oral doses, respectively.