A comparison of the effects of two antispastic drugs, tizanidine and baclofen, on synaptic transmission from muscle spindle afferents to spinal interneurones in cats.
The alpha 2-adrenergic agonist tizanidine was reported to be more efficient than baclofen in reducing muscle tone in some spastic patients. The aim of this study was to investigate if this might be due to more specific depressive actions of tizanidine on transmission from muscle afferents which contribute to muscle tone. This was done by comparing the effects of tizanidine and baclofen on amplitudes of monosynaptic spinal focal field potentials produced by stimulation of muscle nerves in the cat. Such field potentials were recorded in the intermediate zone of the fourth lumbar segment, where they display two distinct components, an early one from group I afferents and a later one from group II afferents. Both reflect EPSPs produced in interneurones in disynaptic pathways to motoneurones. Tizanidine strongly depressed potentials caused by group II afferents, while it had no effect or slightly facilitated potentials produced by group I afferents. In contrast, baclofen had inconsistent effects on the group II potentials; in some cases it caused a depression and in others it caused only an increase in the latency and time to peak, at doses that strongly and consistently depressed the group I potentials. These effects have been found after both local and systemic applications. The antispastic actions of tizanidine may therefore only be related to the depression of transmission from group II muscle afferents, while antispastic actions of baclofen may be secondary to the depression of any sensory fibres. Since tizanidine is as effective in depressing spasticity as baclofen, it is suggested that the enhancement in synaptic transmission from group II muscle afferents may play an important role in the development of exaggerated stretch reflexes in spastic patients.
Skoog
B
B
Department of Physiology and Pharmacology, Göteborg University, Sweden.
D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001418:Baclofen / Q000494:pharmacology*; D002415:Cats; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007395:Interneurons / Q000187:drug effects; D009470:Muscle Spindles / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D000927:Anticonvulsants; C023754:tizanidine; D001418:Baclofen; D003000:Clonidine