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

Content Provider	PubMed Central
Author	Parsons, Andrew A. Bingham, Sharon Raval, Pravin Read, Simon Thompson, Mervyn Upton, Neil
Copyright Year	2001
Abstract	The effects of tonabersat (SB-220453) were evaluated on trigeminal nerve ganglion stimulation-induced sensory-autonomic neurovascular reflexes in the anaesthetized cat. Comparisons were made to intravenous administration of carabersat (SB-204269), and to valproate, gabapentin and lamotrigine following intraduodenal administration. There were no effects on resting blood pressure, heart rate, carotid blood flow or carotid vascular resistance for any compound evaluated. Trigeminal nerve ganglion stimulation increased carotid blood flow by 65% and reduced vascular resistance by 41% with minimal effect on blood pressure (<10%) and no effect on heart rate. Intravenous infusion of tonabersat or carabersat (both 3.4 μmol h−1) produced time related reductions in stimulation-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 μmol h−1) produced a similar inhibitory effect (32±9%, n=4) after 120 min of infusion. Following intraduodenal administration of tonabersat, the maximal inhibition 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). Intraduodenal administration of sodium valproate (10 or 100 mg kg−1 n=4/group) had no effect on neurovascular reflexes. Maximal inhibition of nerve ganglion-stimulated reductions in carotid vascular resistance were observed at 150 min for lamotrigine (50 mg kg−1, 52±12%, n=4) and gabapentin (100 mg kg−1, 17±13%, n=3). Lamotrigine 10 mg kg−1 produced 22±11% (n=3) inhibition after 180 min. These data demonstrate blockade of trigeminal parasympathetic reflexes with tonabersat, carabersat and other anticonvulsants. These agents may therefore have therapeutic benefit in conditions where this type of reflex is evident.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0703932
Ending Page	1557
Page Count	9
Starting Page	1549
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	7
Volume Number	132
Language	English
Publisher Date	2001-04-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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