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Chapter: Modern Pharmacology with Clinical Applications: Local Anesthetics

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Enhancement of Acetylcholine Release

The aminopyridines (4-aminopyridine; 3,4-diaminopyri-dine) accelerate spontaneous exocytosis at central and peripheral synapses.

ENHANCEMENT OF ACETYLCHOLINE RELEASE

Aminopyridines

The aminopyridines (4-aminopyridine; 3,4-diaminopyri-dine) accelerate spontaneous exocytosis at central and peripheral synapses. There is also an increase in the number of transmitter quanta released by a nerve ac-tion potential. This is probably the result of increased Ca++ inflow at the terminals due to a reduction of K+ conductance and prolongation of the nerve action po-tential. Muscle strength is increased in patients with the Lambert-Eaton myasthenic syndrome and in others poisoned with botulinum E toxin (discussed later). Improvement in uncontrolled spasms, muscle tone, and pulmonary function is noted in patients with multiple sclerosis or long-standing spinal cord damage. Side ef-fects that limit clinical utility include convulsions, rest-lessness, insomnia, and elevated blood pressure. Of the two agents, 3,4-diaminopyridine is the more potent and crosses the blood-brain barrier less readily.

Guanidine

Guanidine hydrochloride is the drug of choice in the management of patients with myasthenic syndrome and may be of use in the treatment of botulinum intoxication. Its ability to enhance transmitter release may involve a block of K+ channels and prolongation of the nerve ac-tion potential.

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