The tolerability and pharmacokinetics of the novel antimigraine compound 311C90 in healthy male volunteers

1 311C90 is a novel and selective agonist at 5‐HT_1D receptors, with central and peripheral actions, currently in development for the acute oral treatment of migraine.

2 The pharmacokinetic and tolerability profiles of single oral doses from 1–50 mg 311C90 were investigated in 12 healthy male volunteers in a double‐blind, placebo‐controlled, dose‐escalating study.

3 311C90 was well tolerated with most adverse experiences of mild and transient nature.

4 Absorption was rapid with dose‐independent kinetics. Median t_max was 2–4 h although 50–85% of eventual C_max was attained within 1 h. The t_1/2 was 2.5‐3 h with a high apparent plasma clearance (CL/F > 2000 ml min^‐1) and apparent volume of distribution (V_Z/F) of 400–5001.

5 Three metabolites were detected in plasma and urine, one of which, the N‐desmethyl metabolite, has 5‐HT_1D agonist activity.

6 311C90 showed no clinically significant effects on blood pressure, heart rate, ECG or laboratory variables at any dose and demonstrated a tolerability and pharmacokinetic profile compatible with an acute oral migraine treatment.

DOI: 10.1111/j.1365-2125.1996.tb00172.x

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