How would you counteract the effects on an antagonist on the post synaptic neuron?… by Lady
Specifically to combat strychnine? Would you use an agonist? Why and how would this work?
I'm looking for the pharmalogical approach to counteract the effects. Specifically at the synaptic level – would you introduce an agonist? A beta blocker?
Best Answer:
Sorry about this being so wordy, but it's tricky to follow without a thorough description.
From http://ccforum.com/content/6/5/456 “The mechanism of action causing strychnine toxicity is well understood. This poison is a competitive antagonist of the inhibitory neurotransmitter glycine at receptors in the spinal cord, brain stem and higher centres.”
This means that strychnine interferes with glycine, a neurotransmitter released from the presynaptic neurons of several parts of the nervous system into synapses to activate glycine receptors on the post synaptic neuron and in so doing, prevent those postsynaptic neurons from firing (inhibitory effect of glycine).
When strychnine is present, the glycine can't inhibit the post-synaptic neurons, which fire excessively, perhaps causing twitching, tremors and muscular contractions. Notice that strychnine is antagonizing an inhibitor (glycine), so it is facilitating the post-synaptic neuron, not inhibiting it.
Theoretically, you could antagonize this effect with something that competes with the strychnine for the post-synaptic receptors. If you could get hundreds of glycine molecules (or any other molecule capable of stimulating the glycine receptor, a so-called glycine receptor agonist) into the synapse for every strychnine molecule already there, you could antagonize the strychnine by diluting its presence and its effect. This is called competitive inhibition, and yes, it would be by using a glycine receptor AGONIST.
—THIS WOULD BE THE END OF THE ANSWER IF IT WAS POSSIBLE TO DO. MORE ON WHAT IS REALLY DONE FOLLOWS—
If it was possible to do, you could also antagonize the strychnine with any substance that chews it up or chemically alters it to reduce the amount of active strychnine in the synapses. No such chemical is known.
In practice, what is done is pancuronium is given, which is a competitive inhibitor not of the synapse between two neurons that we have been talking about, but of the synapse between the post-synaptic neuron and the muscle that it innervates preventing the muscle from contracting when the post-synaptic neuron overly stimulates it. This causes paralysis, which is what we want when the problem is excessive muscular contraction.
Of course, we need to breath for the patient with a mechanical ventilator after paralyzing him with pancuronium.
Notice that we have been talking about two synapses. One is between the first nerve and the second nerve. This is where the glycine and strychnine are able to work. We also have a second synapse between the second neuron and the muscle it stimulates. In reality, it is acetylcholine that is released here to stimulate the muscle, and it is acetylcholine that pancuronium competitively inhibits by getting onto the muscle receptor and blocking the acetylcholine from doing it's muscle stimulation thing without stimulating the blocked receptor. This makes pancuronium a competitive inhibitor of the acetylcholine like the glycine was to the strychnine, but instead of it being an agonist for the receptor like the glycine was (glycine stimulates the receptor and inhibits the next neuron), pancuronium is an acetylcholine antagonist.
From http://www.templejc.edu/dept/ems/drugs/pancuronium.html
“Pancuronium produces complete muscular relaxation by binding to the nicotinic M receptors for acetylcholine at the neuromuscular junctions, without initiating depolarization of the muscle membrane.”
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