Antispasticity drugs

FIGURE 13-2 Structure of three primary antispasticity drugs. 

Rehabilitation specialists also play a critical role in helping patients adapt to sudden changes in muscle excitability caused by antispasticity drugs. Reducing spasticity may, in fact, adversely affect the individual relying on increased muscle tone to assist in functional activities... 

Therapists can therefore play a vital role in facilitating the substitution of normal physiologic motor control for the previously used spastic tone. This idea seems especially true when one of the parenteral antispasticity techniques is used, such as intrathecal baclofen or botulinum toxin injections. For example, patients who receive intrathecal baclofen through programmable pump systems often require a period of intensive rehabilitation to enable the benefits from decreased spasticity and increased voluntary motor function to occur. Therapists must therefore be ready to use aggressive rehabilitation techniques to help patients adapt to the relatively rapid and dramatic decrease in muscle tone that is often associated with antispasticity drug therapy. 

Progabide is an antispasticity drug that is also used in the treatment of epilepsy (1). Together with its metabolites, it acts as an agonist at both GABA and GABAb receptors. 

Silperisone (32) is a sodium channel blocker acting centrally as a muscle relaxant. The compormd has been in preclinical animal studies [81, 82] and has been proposed recently to have potential as an antispastic drug in demyelinating diseases such as multiple sclerosis. In vivo, silperisone depressed ventral root reflexes and excitability of motoneurons. Whole-cell measurements in dorsal root ganglion cells revealed that silperisone depressed voltage gated sodium channel conductance at concentrations that inhibited spinal reflexes. 

The second group of antispastic drugs to be developed were the benzodiazepines, typified by diazepam. Diazepam exerts its skeletal muscle relaxant effect by binding as an agonist at the benzodiazepine... 

Montane E, Vallano A, Laporte JR. Oral antispastic drugs in nonprogressive neurologic diseases a systematic review. Neurology 2004 63 1357-1363. 

These drugs have weaker anticholinergic activity than atropine however, they have a significantly more expressed antispastic action. They are used for treating so-called irritable bowel syndrome and diarrhea. 

Adverse effects. Use of diazepam as an antispasticity agent is limited by the sedative effects of this medication that is, patients with spasticity who do not want a decrease in mental alertness will not tolerate diazepam therapy very well. Extended use of the drug can cause tolerance and physical dependence, and use of diazepam for the long-term treatment of spasticity should be avoided whenever possible.102... 

Alpha-2 receptors have also been identified on interneurons in the spinal cord. Stimulation of these receptors causes interneuron inhibition, and a subsequent decrease in excitability of motor neurons supplied by the interneurons.6,8 Alpha-2 agonists have therefore been used to normalize neuronal activity in conditions such as spasticity the use of these drugs as antispasticity agents is discussed in more detail in Chapter 13. 

A variety of drugs with antiepileptic, antispastic, or antidepressant activity are used to manage cranial neuralgias. These compounds are usually more useful than agents with general analgesic properties. 

The documentation of adverse effects is still fragmentary. Tizanidine seems to be a relatively well tolerated and useful antispastic agent. The most frequently reported adverse effects include drowsiness, dry mouth, and muscle weakness (3). Occasionally, hypotension can occur it is usually mild (4,5) but can be more severe in patients taking antihypertensive drugs (6-8), in whom tizanidine should be used with great caution. A small fall in heart rate has also been reported (9). 

Some interesting applications of the conjugate addition of malonates to nitroolefins are the stereoselective synthesis of the antispastic agent (/ )-Baclofen [238b], and the antidepressant drug (/ )-rolipram, the latter obtained via highly stereoselective conjugate addition of a malonic acid half-thioester to a nitrostyrene derivative catalyzed by urea 154 [242],... 

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