Available online at www.sciencedirect.com Neuroscience Letters 433 (2008) 170–173 Dose-dependent effect of carbamazepine on weanling rats submitted to subcutaneous injection of tityustoxin Patr´ ıcia Alves Maia Guidine a , Gioconda Assumpc ¸˜ ao a , Tasso Moraes-Santos b , Andr´ e Ricardo Massensini a , Deocl´ ecio Alves Chianca Jr. c , M´ arcio Fl´ avio Dutra Moraes a,∗ a N´ ucleo de Neurociˆ encias (NNC), Departamento de Fisiologia e Biof´ ısica, Instituto de Ciˆ encias Biol ´ ogicas, Universidade Federal de Minas Gerais, Av. Antˆ onio Carlos, 6627, Pampulha, 31270 901 Belo Horizonte, Minas Gerais, Brazil b Laborat´ orio de Nutri¸ c˜ ao Experimental (LNE), Faculdade de Farm´ acia, Universidade Federal de Minas Gerais, Av. Antˆ onio Carlos, 6627, Pampulha, 31270 901 Belo Horizonte, Minas Gerais, Brazil c Laborat´ orio de Fisiologia Cardiovascular (LFC) - NUPEB, Universidade Federal de Ouro Preto, Campus Universit´ ario - ICEB II, 35400 000 Ouro Preto, Minas Gerais, Brazil Received 6 November 2007; received in revised form 21 December 2007; accepted 27 December 2007 Abstract The scorpion envenoming syndrome is a serious public health matter in Brazil. The most severe cases occur during childhood and elderly. Previous results from our laboratory suggest that the effects of scorpion toxins on the central nervous system play a major role on the lethality induced by scorpion envenoming. The aim of this work is to evaluate the therapeutic potential of carbamazepine (CBZ) injected i.p. 90 min before s.c. tityustoxin (TsTX) injection in weanling rats. Rats were divided into six experimental groups according to s.c. injection (saline or TsTX) and i.p. treatment (vehicle or CBZ 12, 50 and 100mg/kg): Sal/Veh group (n = 4); Sal/CBZ100 (n = 4); TsTX/CBZ12 (n = 6); TsTX/CBZ50 (n = 8); TsTX/CBZ100 (n =8) and, at last, TsTX/Veh (n = 8). The dose of TsTX was the same for all groups: 6.0 mg/kg, twice the DL50 for weanling rats. Video images were recorded until death or for a maximum period of 240min. Lungs were excised and weighed to evaluate edema. The results showed that CBZ (12, 50 and 100mg/kg) was able to increase the survival rate and latency-to-death of the rats. Only the group treated with 100 mg/kg of CBZ had a decrease in the pulmonary edema. The known effect of CBZ reducing neuronal excitability most likely protected the neural substrates targeted by TsTX. Although treatment was performed before TsTX inoculation, the results are promising regarding CBZ as a therapeutic coadjuvant in the treatment of scorpion poisoning. The pharmacokinetics of CBZ can be very much improved by either changing the form of administration or encapsulating the drug in order to enhance solubility. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Tityustoxin; Carbamazepine; Neuroprotection; Scorpion envenoming The scorpion envenoming syndrome is a serious public health matter with high prevalence in tropical countries. In Brazil, there are 8000 accidents notified per year, with an incidence of three cases for each 100,000 inhabitants. Tityus serrulatus is respon- sible for the most serious accidents [12]. Clinical symptoms of the envenoming depend on the type of accident, body region of venom inoculation and the age of the patient. The consequences can vary from mild or moderate local pain and paresthesia (90% ∗ Corresponding author at: N´ ucleo de Neurociˆ encias, Department of Phys- iology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antˆ onio Carlos, 6627 – CEP 31270-901 – Campus Pampulha, Belo Horizonte, MG, Brazil. Tel.: +55 31 3499 2930; fax: +55 31 3499 2924. E-mail address: mfdm@icb.ufmg.br (M.F.D. Moraes). from envenoming accidents) to serious systemic dysfunctions such as cardiac arrhythmias, gastrointestinal alterations, lung edema, pancreatitis, convulsions, neurological lesions, coma and even death [30,10]. The most serious envenoming cases occur in children and in senior subjects [19]. Scorpion antivenom is indicated in 10% of the cases [12], considered as severe scorpion envenoming. However, even with treatment, there is a general lethality of 0.6% prevailing in children under 6 years old. Tityus serrulatus scorpion venom consists of a complex mix- ture of toxic and non-toxic peptides. Two types of toxins within the venom have been proposed as responsible for its toxic effects: toxin gamma (a -type toxin) and tityustoxin (TsTX, an -type toxin), both with specific affinity to the voltage-gated sodium channels (VGSCs) [2]. The toxin used in this study, TsTX, has 0304-3940/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2007.12.059