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  • Title: Depression by flupirtine, a novel analgesic agent, of motor and sensory responses of the nociceptive system in the rat spinal cord.
    Author: Carlsson KH, Jurna I.
    Journal: Eur J Pharmacol; 1987 Nov 03; 143(1):89-99. PubMed ID: 3691652.
    Abstract:
    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.
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