RT journal article
T1 Photoswitchable Carbamazepine Analogs for Non-Invasive Neuroinhibition In Vivo
A1 Camerin, L.
A1 Maleeva, G.
A1 Gomila, A.M.J
A1 Suárez-Pereira, Irene
A1 Matera, C.
A1 Prischich, D.
A1 Opar, E.
A1 Riefolo, F.
A1 Berrocoso Domínguez, Esther María
A1 Gorostiza, P.
A2 Neurociencias
A2 Psicología
K1 azobenzene
K1 diazocine
K1 epilepsy
K1 neuromodulation
K1 pain
K1 photopharmacology
K1 tricyclic drugs
AB A problem of systemic pharmacotherapy is off-target activity, which causes adverse effects. Outstanding examples include neuroinhibitory medications like antiseizure drugs, which are used against epilepsy and neuropathic pain but cause systemic side effects. There is a need of drugs that inhibit nerve signals locally and on-demand without affecting other regions of the body. Photopharmacology aims to address this problem with light-activated drugs and localized illumination in the target organ. Here, we have developed photoswitchable derivatives of the widely prescribed antiseizure drug carbamazepine. For that purpose, we expanded our method of ortho azologization of tricyclic drugs to meta/para and to N-bridged diazocine. Our results validate the concept of ortho cryptoazologs (uniquely exemplified by Carbazopine-1) and bring to light Carbadiazocine (8), which can be photoswitched between 400–590 nm light (using violet LEDs and halogen lamps) and shows good drug-likeness and predicted safety. Both compounds display photoswitchable activity in vitro and in translucent zebrafish larvae. Carbadiazocine (8) also offers in vivo analgesic efficacy (mechanical and thermal stimuli) in a rat model of neuropathic pain and a simple and compelling treatment demonstration with non-invasive illumination.
PB John Wiley and Sons Inc
SN 1521-3773
YR 2024
FD 2024
LK http://hdl.handle.net/10498/35768
UL http://hdl.handle.net/10498/35768
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-may-2026