Flupirtine : it's mechanism of action and its use in the treatment of spasticity

Plummer, Chris (1992). Flupirtine : it's mechanism of action and its use in the treatment of spasticity Other, Department of Medicine, The University of Queensland.

       
Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
THE8086.pdf Full text application/pdf 7.81MB 1
Author Plummer, Chris
Thesis Title Flupirtine : it's mechanism of action and its use in the treatment of spasticity
School, Centre or Institute Department of Medicine
Institution The University of Queensland
Publication date 1992
Thesis type Other
Supervisor Prof. M. Eadie
Prof. Diener
Total pages 115
Language eng
Formatted abstract
Flupirtine maleate (Katadolon) is a known centrally acting analgesic. Recent animal experiments have uncovered an additional muscle relaxant property of the drug. This has raised the question of a possible application for flupirtine in the treatment of spasticity. As such, the present study is the first to investigate the proposed antispastic effects of the drug in human subjects.

Three methods of investigation were used : dynamic posturography, H reflex testing, and flexor reflex testing. Flupirtine was given in a single oral 400 mg dose.

Dynamic posturography (NeuroCom) was carried out on 16 normals and on 5 patients with clinical spasticity. Subjects stood on a moveable forceplate which was tilted upwards around the ankle axis (4 ° at 50 °/s). Short and medium latency reflex responses (SL and ML) were recorded in the gastrocmedialis muscle of triceps surae. A long latency response (LL) was found to occur in the antagonist tibialis anterior muscle. Flupirtine markedly decreased the size of the ML reflex in normals. ML is believed to be a segmental polysynaptic response. Abnormally delayed LL latencies in patients were seen before administration of flupirtine and were attributed to changes in reciprocal inhibition and/or to delayed conduction in transcortical reflex pathways.

In the same patient group, flupirtine was not associated with a decrease in muscle tone as measured by the resistance to passive muscle stretch. Tendon jerks also remained unaltered.

H reflexes were elicited in soleus muscle by electrical stimulation of the tibial nerve in the popliteal fossa. There was no significant change in either the H reflex latency or the Hmax/Mmax ratio for 6 normals. Hmax/Mmax references the maximum H reflex amplitude to the amplitude of the maximum motor response recordable in soleus. This result supports earlier findings that flupirtine does not act on spinal monosynaptic pathways.

Flexor reflex testing involved stimulation of the tibial nerve behind the medial malleolus at 2 times motor threshold. EMG activity was recorded from the tibialis anterior muscle in 7 normals. Both components of the flexor response (Fl and F2) were significantly depressed by flupirtine. This is in agreement with results obtained from animal experiments. The flexor reflex is a polysynaptic segmental response.

The present study provides evidence consistent with flupirtine acting on polysynaptic spinal pathways. Peak effects for flexor and postural ML reflexes were measured at 2 hours.

Elucidation of the drug's use in the treatment of spasticity will require testing on a larger patient group. However, the present results for 5 patients with slight to moderate spasticity cannot support a role for flupirtine as a muscle relaxant. Although flupirtine significantly decreased flexor reflex activity in normals, it remains to be seen whether the drug can relieve flexor spasms which typically occur in more severe cases of spasticity.

Keyword Spasticity.
Neuromuscular transmission.
Neuromuscular diseases.

Document type: Thesis
Collection: UQ Theses (non-RHD) - UQ staff and students only
 
Citation counts: Google Scholar Search Google Scholar
Created: Wed, 21 Sep 2011, 17:43:35 EST by Ms Christine Heslehurst on behalf of Scholarly Communication and Digitisation Service