Carabersat

Names

[ Name ]:
Carabersat

[Synonym ]:
carabersat
CARABERSAT
trans-4-(4-fluorobenzoylamino)-6-acetyl-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ol
trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3R-ol
trans-(+)-6-acetyl-4S-(4-fluorobenzoylamino)-3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3R-ol

Biological Activity

[Description]:

Carabersat is a potent anticonvulsant agent.

[Related Catalog]:

Signaling Pathways >> Others >> Others

Research Areas >> Neurological Disease

[In Vitro]

[3H]Carabersat ([3H]SB 204269) binds to rat forebrain membranes with moderate affinity (Kd 40 nM) and pKi values of 7.3[1]. Carabersat is able to bind to mouse forebrain membranes, and the binding is saturable and stereospecific, with a Kd of 53 nM. The labelled [3H]Carabersat produces a Kd of 32 nM[2]. Carabersat (SB-204269, 1-100 μM) has no effect on Na+ current in cultured hippocampal neurones. Carabersat also shows no effect on action potential discharges evoked by elevating external K+[3]. Carabersat (SB-204269) is structurally-related to the benzopyran ATP-sensitive potassium channel (KATP) opener, cromakalim, but has opposite stereochemistry, and the mechanism of action of Carabersat is not thought to involve KATP[4].

[In Vivo]

Carabersat (5b) significantly elevates anticonvulsant activity in mice[1].

[Animal admin]

Mice[1] In this model, groups of 10-20 naive mice (25-30 g) are assessed for production of a tonic hindlimb extension seizure following a single corneal electroshock using an "up and down" method of shock titration. The effects of drug treatment are expressed as a percentage change from vehicle control values and statistical comparisons between groups are made. Carabersat is administered orally as a fine suspension in 1% methylcellulose one hour before electroshock application[1].

[References]

[1]. Wai N. Chan, et al. Synthesis of Novel trans-4-(Substituted-benzamido)-3,4-dihydro-2H-benzo[b]pyran-3-ol Derivatives as Potential Anticonvulsant Agents with a Distinctive Binding Profile. J. Med. Chem., 1996, 39 (23), pp 4537-4539.

[2]. Herdon H, et al. The novel anticonvulsant SB 204269 binds to a stereospecific site in the mouse brain. Eur J Pharmacol. 1996 Oct 31;314(3):R7-8.

[3]. Caeser M, et al. Lack of effect of the novel anticonvulsant SB-204269 on voltage-dependent currents in neurones cultured from rat hippocampus. Neurosci Lett. 1999 Aug 13;271(1):57-60.

[4]. Crespi F, et al. SB-204269 SmithKline Beecham. IDrugs. 1998 Sep;1(5):595-8.

[Related Small Molecules]