Changes in seizure susceptibility to local anesthetics by repeated administration of cocaine and nomifensine but not GBR12935: possible involvement of noradrenergic system.
We examined cross-sensitization of cocaine and synthetic local anesthetics to their seizure susceptibility after repeated administration. Seizure susceptibility of procaine and lidocaine increased after the end of two days of treatment with a subconvulsive dose of cocaine. Acute treatment with nomifensine but not GBR12935, a specific inhibitor of the dopamine transporter, facilitated lidocaine-induced convulsion. Furthermore, daily treatment with nomifensine for two days enhanced lidocaine-induced convulsion. These results suggest the possible involvement of the brain noradrenergic system in the changes in seizure susceptibility after repeated administration of some local anesthetics.
Sato
T
T
Department of Pharmacology, Hiroshima University School of Dentistry, Japan.
Kitayama
S
S
Morita
K
K
Ikeda
T
T
Dohi
T
T
D000779:Anesthetics, Local / Q000009:adverse effects*; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009627:Nomifensine / Q000008:administration & dosage / Q000009:adverse effects*; D009638:Norepinephrine / Q000502:physiology*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D012640:Seizures / Q000139:chemically induced*
D000779:Anesthetics, Local; D010879:Piperazines; D009627:Nomifensine; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D003042:Cocaine; D009638:Norepinephrine