Nicotinic receptors activation

Galantamine 18% 7 CYP 2D6 substrate CYP 3A4 substrate Allosteric nicotinic receptor activity Once-daily dosing for extended-release formulation... 

It is a broad spectrum anthelmintic effective in pinworm, ascariasis and hook worm infestation. It exerts its action by producing persistent nicotinic receptor activation which results in spastic paralysis of worms. 

Bethanechol Muscarinic agonist t negligible effect at nicotinic receptors Activates Mi through M3 receptors in all peripheral tissues causes increased secretion, smooth muscle contraction (except vascular smooth muscle relaxes), and changes in heart rate Postoperative and neurogenic ileus and urinary retention Oral and parenteral, duration 30 min does not enter central nervous system (CNS) Toxicity Excessive parasympathomimetic effects, especially bronchospasm in asthmatics Interactions Additive with other parasympathomimetics... 

Drew AE, Werling LL. 2001. Protein kinase C regulation of dopamine transporter initiated by nicotinic receptor activation in slices of rat prefrontal cortex. J Neurochem 77 839-848. 

The main use of drugs at the neuromuscular junction is to relax muscle in anaesthesia, or to inhibit acetylcholinesterase in diseases where nicotinic receptor activation is reduced.e.g. myasthenia gravis. 

Hihnas C, Pereira EL, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX (2001) The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression Physiopathological implications. J Neurosci 21 7463-7473. 

Excess synaptic acetylcholine stimulates muscarinic receptors (peripheral and CNS) and stimulates but then depresses or paralyzes nicotinic receptors." Activation of peripheral muscarinic receptors causes signs and symptoms described by the mnemonics SLUDGE or DUMB BELS, defined earlier. 

The actual signs and symptoms observed depend on the balance of muscarinic and nicotinic receptor activation. While miosis (muscarinic action) is most common, it may not always be present, and indeed mydriasis (nicotinic action) may occur. Likewise tachycardia (nicotinic effect) may be present rather than bradycardia (muscarinic action). Death most commonly results from respiratory failure, a consequence of nicotinic receptor-mediated muscle paralysis, combined with muscarmic-facilitated bronchorrhea, bronchoconstriction, and CNS depression. 

Table 11-2-2 summarizes the effects of nicotinic receptor activation on the adrenal medulla, the autonomic ganglia, and the neuromuscular junction. The effect of autonomic ganglia stimulation depends upon the transmission system used to conned the ganglia to the end organ. Blood vessels are innervated by SANS, resulting in vasoconstriction. PANS innervates the gut, the end result being increased motility and secretion. 

FIGURE 9-3 Pharmacology of the neuromuscular junction. The modification of excitation-ACh secretion and nicotinic receptor activation-contraction coupling by various agents is shown on the right an arrow marked with an X indicates inhibition or block a plain arrow indicates enhancement or activation. 

Schoffelmeer ANM, De Vries TJ, Wardeh G, van de Ven HWM, Vanderschuren LJMJ (2002) Psychostimulant-Induced Behavioral Sensitization Depends on Nicotinic Receptor Activation. J Neurosci 22 3269... 

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