Pharmacology of the Motor System

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The lower motor neuron uses acetylcholine as its neurotransmitter. The internuncial pool of neurons in the spinal cord are all inhibitory neurons that use the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glycine. Whereas glutamate is the most important excitatory neurotransmitter in the brain as well as the motor system, GABA is the most widely distributed and major chemical neurotransmitter used in the inhibitory systems. Some output neurons in the basal ganglia and cerebellum use GABA as their transmitter, but most GABA is contained and utilized by local circuit inhibitory interneurons including the internuncial pool in the spinal cord. GABA is synthesized from glutamate by the enzyme glutamic acid decarboxylase (GAD) and is catabolized by the enzyme GABA-transaminase (GABA-t). Drugs that inhibit GABA-t such as some newly developed antiepileptic drugs increase the concentrations of GABA and inhibitory tone. Drugs can also act as agonists at GABA receptors. Clinically useful drugs such as the benzodiazepines and baclofen presumably reduce spasticity by stimulating GaBa receptors at inhibitory synapses in the spinal cord.y Toxins and poisons like tetanus toxin and the drugs picrotoxin and bicuculline block GABA receptors, thereby producing excessive

Figure 15-19 (Figure Not Available) The rubrospinal trac(From Snell RS: Clinical Neuroanatomy for Medical Students. Boston, Little, Brown & Co., Inc., 1987.)

Figure 15-20 (Figure Not Available) DecorticatffA) and decerebrate(B) posturing. (From Plum F, Posner JB: Diagnosis of Stupor and Coma. Philadelphia, F. A. Davis, 1980.)

excitation and leading to tetanic muscle spasms or convulsions.

Glycine is the principal neurotransmitter of the Renshaw cell. Strychnine is a specific antagonist at the glycine receptor. In small doses strychnine has been used as part of herbal or homeopathic preparations as an "energizer." In higher concentrations it causes convulsions by blocking normal inhibitory feedback on the motor neurons.

The motor neurons of the cerebral cortex use glutamate as their transmitter. This includes all motor outputs from the cerebral cortex including the corticospinal and corticobulbar tracts as well as inputs to the rubrospinal and tectospinal systems. Aspartate has also been proposed as a neurotransmitter at some of the synapses, but evidence favoring it is much less compelling than favoring glutamate.


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