Articles: analgesics.
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The antinociceptive activity of flupirtine was measured in various test procedures predictive of analgesic activity. In the electrostimulated pain test in mice the oral ED50 for flupirtine was 25.7 mg/kg p.o. Thus, flupirtine was approximately 31.7 times more potent than paracetamol (ED50: 814 mg/kg p.o.) and as potent as pentazocine (ED50: 38.5 mg/kg p.o.). ⋯ Whereas buprenorphine and tramadol showed a striking similarity in the pharmaco-electroencephalogram recorded from different parts of the brain (frontal cortex, thalamus, striatum and the mesencephalic reticular formation) of the freely moving rat, flupirtine was clearly different in action. It produced dose dependent increases in nearly all frequency bands but its effects were different from those of the minor tranquillizer diazepam and the anticonvulsant phenobarbitone. These findings show that the central antinociceptive activity of flupirtine is not based on an opiate mechanism and is not comparable with that of diazepam and phenobarbitone.
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The mechanisms of the antinociceptive action of flupirtine, a novel non-opioid analgesic, were investigated in animals. It was found that this effect could be abolished by pre-treatment with reserpine. Furthermore, it could be dose-dependently antagonized by yohimbine and changes in the EEG of the rat observed after administration of flupirtine were closely related to those obtained after giving clonidine. On these pharmacological results, it is likely that the antinociceptive activity of flupirtine is due to activation of descending noradrenergic pathways.
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Comparative Study
Comparative physical dependence studies in rats with flupirtine and opiate receptor stimulating analgesics.
In physical dependence studies in rats the principle criterion was loss of body weight after withdrawal of the dependence producing drug. Other typical signs of withdrawal were also observed. In contrast to buprenorphine, codeine and tramadol, flupirtine caused no decrease in body weight and no other withdrawal symptoms. Flupirtine does not produce opiate type physical dependence.
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After a brief review of the supraspinal and spinal effects of morphine, the reference substance for studies on analgesia, the authors expose a synthesis of the recent literature regarding neurotransmitter involvement in pain perception and transmission. From these data, some future prospects for pain treatment research are identified.