Potentiation of Local Anesthetic Activity of Neosaxitoxin with Bupivacaine or Epinephrine: Development of a Long-Acting Pain Blocker

Abstract

Local anesthetics effectively block and relieve pain, but with a relatively short duration of action, limiting its analgesic effectiveness. Therefore, a long-acting local anesthetic would improve the management of pain, but no such agent is yet available for clinical use. The aim of this study is to evaluate the potentiation of the anesthetic effect of neosaxitoxin, with bupivacaine or epinephrine in a randomized double-blind clinical trial. Ten healthy males were subcutaneously injected into the left and right forearms with a randomized pair of the following treatments: (i) bupivacaine (5 mg); (ii) neosaxitoxin (10 microg); (iii) neosaxitoxin (10 microg) plus bupivacaine (5 mg), and (iv) neosaxitoxin (10 microg) plus epinephrine (1:100.000), but all participant received all four formulations (in 2 ml; s.c.), with 1 month elapsing between the two round of experiments. A validated sensory and pain paradigm was used for evaluating the effect of the treatment 0-72 h after the injections, measuring sensory, pain, and mechanical touch perception threshold. The duration of the effect produced by combined treatments was longer than that by the single drugs. In conclusion, bupivacaine and epinephrine potentiate the local anesthetic effect of neosaxitoxin in humans when co-injected subcutaneously. The present results support the idea that neosaxitoxin is a new long-acting local pain blocker, with highly potential clinical use.

Marked difference in saxitoxin and tetrodotoxin affinity for the human nociceptive voltage-gated sodium channel (Na v 1.7)

“…Given the intense interest in human Na v 1.7 as a target for pain (4)(5)(6)(7)15) and growing interest in clinical applications of guanidinium toxins as antinociceptive agents (16)(17)(18)(19)(20)(21)(22)(23), we began a series of electrophysiology recordings with TTX, STX, and gonyautoxin-III (GTX-III) against recombinant hNa v 1.7 α-subunit expressed in CHO cells. For comparative purposes, an identical series of measurements was made using rat Na v 1.4 (CHO).…”

Comparison of Neosaxitoxin Versus Bupivacaine via Port Infiltration for Postoperative Analgesia Following Laparoscopic Cholecystectomy

“…Previous studies of several site 1 toxins in animals 8,14,15 and a study of neoSTX-bupivacaine and neoSTX-epinephrine combinations for subcutaneous infiltration in human volunteers 30 indicated that combination formulations involving a site 1 toxin such as neoSTX plus either bupivacaine or epinephrine produce more intense and more prolonged analgesia compared with neoSTX alone. Future clinical trials of such combinations are planned.…”

Chronic Toxicity Study of Neosaxitoxin in Rats

“…On the other hand NeoSTX has a selective blocking effect over NA V 1.2 [10,11]. This pharmacodynamical difference can explain the long lasting effect of NeoSTX that provides analgesia for over 24 h in animals and human volunteers [12,13]. …”