Depression by flupirtine, a novel analgesic agent, of motor and sensory responses of the nociceptive system in the rat spinal cord.

The analgesic agent, flupirtine, was tested on motor and sensory responses of the nociceptive system in rats. The motor response was determined in the tail-flick test with radiant heat. The sensory response was determined as activity evoked in ascending axons by electrical stimulation of nociceptive afferents in the sural nerve. The tail-flick latency was dose dependently increased by flupirtine administered by intraperitoneal (i.p.) injection (ED50 7.8 mg/kg), intrathecal (i.t.) injection (ED50 14.8 micrograms/rat) or bilateral microinjection into the periaqueductal grey (PAG; ED50 2.6 micrograms/rat). Naloxone reduced the effect of an i.p. injection of flupirtine but was ineffective against an i.t. injection of the drug. The activity in ascending axons responding to afferent C fibre stimulation was depressed by flupirtine administered by intravenous (i.v.) injection (7 mg/kg) under urethane anaesthesia with an intact spinal cord and brain, and by i.t. injection (14 micrograms/rat) to decerebrated spinal rats. Naloxone did not abolish the depressant effect of i.t. injections of flupirtine. Microinjection of flupirtine (1.7 micrograms/rat) made in the PAG did not reduce, but increased the spontaneous and C fibre-evoked activity in ascending axons. The results indicate that flupirtine selectively depresses responses of the nociceptive system by a spinal (motor and sensory responses) and a supraspinal (motor response) action in which opiate-like mechanisms play no or a minor role.