Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes

1 The effects of tonabersat (SB-220453) were evaluated on trigeminal nerve ganglion stimulation-induced sensory-autonomic neurovascular reflexes in th e anaesthetized cat. Comparisons were made to intravenous administration of carabersat (SB-204269), and to valproate, gabapentin and lamotrigine follo wing intraduodenal administration. 2 There were no effects on resting blood pressure, heart rate, carotid bloo d flow or carotid vascular resistance for any compound evaluated. 3 Trigeminal nerve ganglion stimulation increased carotid blood flow by 65% and reduced vascular resistance by 41% with minimal effect on blood pressu re (<10%) and no effect on heart rate. Intravenous infusion of tonabersat o r carabersat (both 3.4 <mu>mol h(-1)) produced time related reductions in s timulation-induced responses with a maximal inhibition (relative to control ) of 30 +/- 7% (n = 4), at 240 min for tonabersat and 33 +/- 4% (n = 3) at 180 min for carabersat. Tonabersat (11.5 mu mol h(-1)) produced a similar i nhibitory effect (32 +/- 9%, n = 4) after 120 min of infusion. 4 Following intraduodenal administration of tonabersat, the maximal inhibit ion of nerve stimulation-induced responses was 55 +/- 4% at 120 min (n = 4) for tonabersat 10 mg kg(-1), and 24 +/- 2% after 180 min for 1 mg kg(-1) ( n = 4). 5 Intraduodenal administration of sodium valproate (10 or 100 mg kg(-1) n = 4/group) had no effect on neurovascular reflexes. Maximal inhibition of ne rve ganglion-stimulated reductions in carotid vascular resistance were obse rved at 150 min for lamotrigine (50 mg kg(-1), 52 +/- 12%, n = 4) and lgaba pentin (100 mg kg(-1), 17 +/- 13%, n = 3). Lamotrigine 10 mg kg(-1) produce d 22 +/- 11% (n = 3) inhibition after 180 min. 6 These data demonstrate blockade of trigeminal parasympathetic reflexes wi th tonabersat, carabersat and other anticonvulsants. These agents may there fore have therapeutic benefit in conditions where this type of reflex is ev ident.