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Drugs Acting on Motor Systems spinal disorders. Benzodiazepines enhance the effectiveness of the inhibitory transmitter GABA (p. 226) at GABAA receptors. Baclofen stimulates GABAB receptors. !2-Adrenoceptor agonists such as clonidine and tizanidine probably act presynaptically to inhibit release of excitatory amino acid transmitters. The convulsant toxins, tetanus toxin (cause of wound tetanus) and strychnine diminish the efficacy of interneuronal synaptic inhibition mediated by the amino acid glycine (A). As a consequence of an unrestrained spread of nerve impulses in the spinal cord, motor convulsions develop. The involvement of respiratory muscle groups endangers life. Botulinum toxin from Clostridium botulinum is the. | 182 Drugs Acting on Motor Systems Drugs Affecting Motor Function The smallest structural unit of skeletal musculature is the striated muscle fiber. It contracts in response to an impulse of its motor nerve. In executing motor programs the brain sends impulses to the spinal cord. These converge on a-moto-neurons in the anterior horn of the spinal medulla. Efferent axons course bundled in motor nerves to skeletal muscles. Simple reflex contractions to sensory stimuli conveyed via the dorsal roots to the motoneurons occur without participation of the brain. Neural circuits that propagate afferent impulses into the spinal cord contain inhibitory interneurons. These serve to prevent a possible overexcitation of motoneurons or excessive muscle contractions due to the constant barrage of sensory stimuli. Neuromuscular transmission B of motor nerve impulses to the striated muscle fiber takes place at the motor endplate. The nerve impulse liberates acetylcholine ACh from the axon terminal. ACh binds to nicotinic cholinocep-tors at the motor endplate. Activation of these receptors causes depolarization of the endplate from which a propagated action potential AP is elicited in the surrounding sarcolemma. The AP triggers a release of Ca2 from its storage organelles the sarcoplasmic reticulum SR within the muscle fiber the rise in Ca2 concentration induces a contraction of the myofilaments electromechanical coupling . Meanwhile ACh is hydrolyzed by acetylcholinesterase p. 100 excitation of the endplate subsides. If no AP follows Ca2 is taken up again by the SR and the myofilaments relax. Clinically important drugs with the exception of dantrolene all interfere with neural control of the muscle cell A B p. 183ff. Centrally acting muscle relaxants A lower muscle tone by augmenting the activity of intraspinal inhibitory interneurons. They are used in the treatment of painful muscle spasms e.g. in spinal disorders. Benzodiazepines enhance the effectiveness of the inhibitory .
