Safety profile of almotriptan, a new antimigraine agent - Effects on central nervous system, renal function and respiratory dynamics

Almotriptan (3-[2-(dimethylamino)ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl)-1 H-indole, CAS 154323-57-6) is a new 5-HT1B/1D agonist whose clinical effica cy has been demonstrated in Phase III clinical trials. This study aimed to evaluate the safety of almotriptan with respect to the central nervous syst em, renal function and respiratory dynamics using preclinical animal models . The results indicate that almotriptan does not cross the blood-brain barr ier, since no effects on/interaction with spontaneous locomotor activity, h exobarbital-induced sleeping time, caffeine-induced increase of spontaneous locomotor activity, or hypothermia (caused by stimulation of central 5-HT1 D receptors) was observed following treatment. Almotriptan had a mild antie metic effect and a slight, transient diuretic effect In dogs, although the latter effect is probably of no clinical relevance. In addition, no effect on the respiratory system of conscious guinea pigs was observed following a lmotriptan treatment. These results indicate that almotriptan has a favoura ble safety profile with respect to the central nervous, renal and respirato ry systems.