Potent nonopioid antinociceptive activity of telocinobufagin in models of acute pain in mice.

INTRODUCTION: In recent decades, several researches have been conducted in search of new analgesics that do not present the side effects of opioids. In this context, animal venoms contain natural painkillers that have been used for the development of new analgesics. OBJECTIVE: The aims of this study were to evaluate the antinociceptive effects of telocinobufagin (TCB), a bufadienolide isolated from Rhinella jimi venom, in murine acute pain models, and to verify the participation of the opioid system in these effects. METHODS: TCB was purified from R. jimi venom by high-performance liquid chromatography, and its structure was confirmed by spectrometric techniques. TCB was administered intraperitoneally (i.p.) (0.062, 0.125, 0.25, 0.5, and 1 mg·kg-1) and orally (p.o.) (0.625, 1.125, 2.5, 5, and 10 mg·kg-1) in mice, which were then subjected to pain tests: acetic acid-induced writhing, formalin, tail-flick, and hot-plate. Involvement of the opioid system in TCB action was evaluated by naloxone i.p. injected (2.5 mg·kg-1) 20 minutes before TCB administration. In addition, the TCB action on the µ, δ, and κ opioid receptors was performed by radioligand binding assays. RESULTS: In all the tests used, TCB showed dose-dependent antinociceptive activity with more than 90% inhibition of the nociceptive responses at the doses of 1 mg·kg-1 (i.p.) and 10 mg·kg-1 (p.o.). Naloxone did not alter the effect of TCB. In addition, TCB did not act on the µ, δ, and κ opioid receptors. CONCLUSION: The results suggest that TCB may represent a novel potential nonopioid therapeutic analgesic for treatment of acute pains.

Primary structure, behavioral and electroencephalographic effects of an epileptogenic peptide from the sea anemone Bunodosoma cangicum.

The primary structure of cangitoxin (CGX), a 4958 Da peptide from the sea anemone Bunodosoma cangicum, was determined: GVACRCDSDGPTVRGNSLSGTLWLTGGCPSGWHNCRGSGPFIGYCCKK. CGX contains all the 11 residues that are conserved and the 5 that are conservatively substituted within or between the type 1 and type 2 sequences of sea anemone peptides with specific action on voltage-sensitive sodium channels. Furthermore, it also has 6 identities (Asp9, Arg14, Asn16, Leu18, Trp33 and Lys48) and 1 homology (Arg36) in the 8 residues of the pharmacophore of the sea anemone ApB which are essential for interaction with mammalian sodium channels. The intrahippocampal injection of CGX induces several sequential behavioral alterations--episodes of akinesia alternating with facial automatisms and head tremor, salivation, rearing, jumping, barrel-rolling, wet dog shakes and forelimb clonic movements--and the electroencephalography analysis shows that they were followed by important seizure periods that gradually evolved to status epilepticus that lasted 8-12 h, similar to that observed in the acute phase of the pilocarpine model of epilepsy. These results suggest that CGX may be an important tool to develop a new experimental model of status epilepticus which may contribute to understanding the etiology of epilepsy and to test the effects of new antiepileptic drugs.