Local Anesthetic Properties of Prenylamine

Background: Local anesthetics that produce analgesia of long duration with minimal impairment of autonomic functions are highly desirable for pain management in the clinic. Prenylamine is a known calcium channel blocker, but its local anesthetic blocking effects on voltage-gated sodium channels have not been studied thus far. Methods. The authors characterized the tonic and use-dependent prenylamine block of native Na+ channels in cultured rat neuronal GH(3) cells during whole cell voltage clamp conditions and the local anesthetic effect of prenylamine by neurologic evaluation of sensory and motor functions of sciatic nerve during neural block in rats. Results: Prenylamine elicits both use-dependent block of Na+ channels during repetitive pulses (3 muM prenylamine produced 50% block at 5 Hz) and tonic block for both resting and inactivated Na+ channels. The 50% inhibitory concentration for prenylamine was 27.6 +/- 1.3 muM for resting channels and 0.75 +/- 0.02 muM for inactivated channels. Furthermore, in vivo data show that 10 nim prenylamine produced a complete sciatic nerve block of motor function, proprioceptive responses, and nociceptive responses that lasted approximately 27, 34, and 24 h, respectively. Rats injected with 15.4 mm bupivacaine, a known local anesthetic currently used for pain management, had a significantly shorter duration of blockade (< 2 h) compared with rats injected with prenylamine. Conclusions: The data presented here demonstrate that prenylamine possesses local anesthetic properties in vitro and elicits prolonged local anesthesia in vivo.