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I am thinking how pyridostigmine can be used in the treatment of myasthenia gravis. Its similar compound (neostigmine) is also anticholine esterase. This compound has the indication of myasthenia gravis but with the stimulation of the nicotinic receptor.

I cannot understand how pyridostigmine is causing the effect. Probably, pyridostigmine is similar to neostigmine in structure, which can be why more pieces of information is about neostigmine than pyridostigmine.

How can pyridostigmine have the indication of myasthenia gravis?

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Pyridostigmine is an analog of neostigmine, so has the same basic mechanism of action. Please forgive me for repeating information you may already know.

There are two main families of acetylcholine receptors: muscarinic and nicotinic. Acetylcholine receptors at the neuromuscular junction (NMJ) are exclusively nicotinic (N1 or NM), so that's the only receptor I'll address.

Myasthenia Gravis is caused by an immune response to nicotinic postsynaptic receptors on skeletal muscle. An antibody can either destroy or block the receptor site. The antibodies destroy the receptor sites more rapidly than the body can replace them. In MG, there can be as much as an 80% reduction in the number of these receptor sites.

Acetylcholinesterase (AChE) is an enzyme that breaks down acetylcholine (ACh) at the synaptic cleft. AChE has a remarkably high specific catalytic activity: each molecule of AChE degrades about 25000 molecules of ACh per second. Any drug which serves to inhibit AChE will increase ACh concentration at the N1 receptor. AChE inhibitors can be irreversible or reversible. Reversible inhibitors, (competitive or noncompetitive) have therapeutic applications; irreversible AChE modulators are toxic.

Carbamates are organic compounds derived from carbamic acid (NH2COOH). They are reversible AChE inhibitors. This group includes neostigmine, pyridostigmine and physostigmine. Pyridostigmine is an analog of neostigmine, so has the same basic mechanism of action. Because they are not lipid soluble, they are selective for the NMJ; both also have direct action on Nm Receptors. The major difference between them is that pyridostigmine has a slight but significantly longer duration of action.

Drug Bank: Pyridostigmine
NeuroLex.org (get's it's info from PubChem)

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  • $\begingroup$ Thank you for your excellent answer with great details! It is never wrong to repeat. Pyridostigmine is parasympathomimetic and reversible cholinesterase inhibitor. These two features seem to work in different directions, but the latter is the main one. It leads to the property of reversing muscle relaxants and its indication of myasthenia gravis. The former effect does not seem to be a major one. -- Let's consider Pilocarpine which is cholinomimetic and exclusively muscarinic (nothing about nicotinic?). It seems that only acetylcholine inhibitors are exclusively nicotinic with (N1 or Nm). $\endgroup$ Dec 4, 2014 at 7:50
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    $\begingroup$ If I'm understanding you correctly (and I'm not sure that I am) pilocarpine is a muscarinic agonist with no nicotinic effects. But there are AChE that are both Nm and muscarinic. $\endgroup$ Dec 4, 2014 at 11:39
  • $\begingroup$ You are understanding me correctly. It seems that also the other short-acting and long-acting AChE are Nm and nicotinic besides neostigmine and pyridostigmine such as ipidacrine, donepezil and rivastigmine. $\endgroup$ Dec 4, 2014 at 12:40

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