1Rats, anaesthetized with urethane, were injected intravenously with dantrolene sodium in a carrier solution of 5% mannitol taken to pH 10 with NaOH. This carrier solution itself was without effect on extrafusal muscle contraction. 2 Dantrolene sodium (5 mg/kg) had a greater depressant action on the twitch contraction of the fast extensor digitorum longus (EDL) muscle than on the slow soleus (SOL) muscle. The EDL twitch was depressed to 25.9% + 1.2% (mean + s.e. mean, n = 7) of control whereas the SOL twitch was depressed to 31.3% + 0.4% (n = 9). These values are significantly different at the P<0.001 level. 3 The twitch contraction time to peak was reduced by approximately 35% in both EDL and SOL by dantrolene sodium. However, the drug reduced the half relaxation time of SOL by approximately 30% but that of EDL was hardly affected. 4 The effect of dantrolene sodium on contractions elicited by repetitive stimulation was dependent upon the stimulation frequency. For the SOL muscle the greatest depression was produced at a stimulation frequency of 25 Hz and for EDL at 75 Hz. The minimum of depression was produced for a full fused tetanus for both muscles. 5 The significance of these findings is discussed in terms of the action of dantrolene sodium on motor control in the intact animal.

SUMMARYTransmission in a pathway mediating presynaptic inhibition of soleus I a afferent terminals was assessed from the reduction of soleus muscle H reflex amplitude brought about by a short conditioning vibration pulse applied to the anterior tibialis muscle. In a group of young subjects (aged between 21 and 37 years) the mean reduction in reflex size with the limb relaxed was to 29-2 % of control, whereas in a group of older subjects (aged between 59 and 74 years) the reduction was significantly less, to 55 0% of control (P < 0 001, Student's t test). In the younger group the amount of presynaptic inhibition elicited was inversely related to the plantar-flexor torque produced by tonic contraction of gastrocnemius-soleus; often at higher torques no reduction in reflex size was seen. In contrast the older group showed only a slight reduction in presynaptic inhibition with increasing torque, so that at torques of 5 and 7 Nm the amount of presynaptic inhibition elicited was similar in the younger and older groups. The older subjects were not able to sustain the higher torques produced by the younger subjects. These results suggest that the control of transmission in this spinal pathway changes with increasing age.

No abstract

In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, and antispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis. An electrogoniometer was used to assess muscle tone at knee extensors, applying Wartenberg Further statistical analysis showed a strong within patient linear correlation between plasma concentrations and antispastic action at 4 and 8 mg doses (p = 0-014 and 0'004 respectively), but only weak between patient correlations. The analysis of the dose-plasma concentration relation showed results consistent with linear pharmacokinetics. The comparison of changes in the R2 ratio with concomitant Ashworth scores showed a significant correlation between the two. It is concluded that there are linear correlations between single doses, plasma concentrations, and antispastic action of tizanidine. Because of the strong within patient but weak between patient correlation between plasma concentrations and antispastic action of tizanidine the effective doses should be determined individually. (9 Neurol Neurosurg Psychiatry 1994;57: 1355-1359 Tizanidine (SirdaludO) is a centrally active a, adrenergic receptor agonist with potent myotonolytic action.l The substance was shown to suppress selectively polysynaptic spinal reflexes while sparing the monosynaptic reflexes.5 Clinical investigations have consistently shown an antispastic effect of tizanidine that was associated with little undue muscle weakness,69 sometimes associated with an improvement in paresis.10 There is, however, little information on the correlation between the antispastic effect and plasma concentrations of tizanidine. ' We report data on the correlations between single doses, plasma concentrations, and antispastic action of tizanidine in patients with spasticity due to multiple sclerosis, by means of an objective quantitative method and a clinical scale for the assessment of spasticity. Methods PATIENT SELECTIONSeventeen patients were entered into the study, but one patient was excluded from further analysis because the baseline severity of spasticity decreased during the study to below that stipulated in the protocol. There were 13 women and four men, mean age 43 (range 24-58) years. All patients had definite multiple sclerosis, diagnosed by clinical criteria and paraclinical investigations. Spasticity had been present for a mean of 70 (range 12-180) months and had been stable for a mean of 17 (range 2-48) months. Extensor spasticity reaching a minimum score of 2 on the Ashworth scale in at least one leg and remaining stable for at least one month was required as an entry criterion. All patients had a baseline score of either 2 or 3 on knee extensors, none had a score of 4, and none of them were bedridden. Patients receiving any drugs with antispastic action, those with significant systemic diseases, local complications, an exacerbation of the disease, or abnormalities in laboratory tests ...

The nerve conduction velocities and motor unit contraction properties of forty‐one hind limb motor units (soleus, 37; extensor digitorum longus, 4) and twenty‐nine motor units from the mid‐tail lateral segmental muscles of the rat were measured. The motor units of the soleus were found to form an homogeneous group as judged by contraction time with just one particularly slowly contracting unit. In the soleus muscle a negative correlation between conduction velocity of the nerve fibre and contraction time of the motor unit was found but no significant correlation between conduction velocity of the nerve fibre and the tetanic tension of the motor unit. The motor units of the tail muscleswere found to form two distinct groups, one of fast units and the other of slow units. In the tail muscles, the slowly conducting motor nerves innervated the slowly contracting units and the fast conducting nerves the fast contracting units. A relationship between the tetanic tension of the tail muscle motor units and nerve conduction velocity was demonstrated.