skeletal muscle relaxants also known as spasmolytic s-- are the drugs that are used to relax or decrease skeletal muscle tone they can act huai two ways they can either act centrally on the central nervous system that is the brain and spinal cord and either they can act peripherally that is directly on the neuromuscular junction the centrally acting skeletal muscle relaxants depress fully synaptic pathways in spinal as well as Supra spinal sites to describe them and discuss their mechanism of action in detail I'll draw an upper motor neuron here acting on a lower motor neuron and this red one will be the inhibitory neuron which will release GABA and regulate skeletal muscle contraction the green one is the lower motor neuron now there will be an action potential from the cerebral cortex via the upper motor neuron into this synapse where there will be the release of any excitatory neurotransmitters such as glutamate or norepinephrine which will then act on the lower motor neuron and thus cause the lower motor neuron to release acetylcholine Anthony rumor spread Junction and contract the skeletal muscle now I'll draw some receptors here the upper motor neuron will have the alpha 2 receptor as the auto receptor the GABA B receptor is present on the lower motor neuron as well as on the upper motor neuron performing different functions the GABA a receptor is present on the lower motor neuron both of these gaba receptors gaba a and gaba B will be acted upon by the inhibitory neuron releasing gaba into the synaptic cleft and this gaba will inhibit the gaba b receptor on the upper motor neuron to stop releasing the excitatory neurotransmitter and on the postsynaptic or the lower motor neuron it will it will act on the GABA B receptor where it will cause hyper-polarization and thus there will be no conduction of the action potential the gaba receptor is also acted upon by the inhibitory neuron releasing gaba and it will act by the same way increasing chloride influx and thus leading to hyper-polarization now that was the physiology now in order for us to develop drugs that act as skeletal muscle relaxants we need to do something that will cause the lower motor neuron to hyperpolarize and not send a signal to the skeletal muscle right now we can do this by three ways firstly we can use the drug designer Dean which will act on the Alpha 2 receptors which are Auto receptors which when will be stimulated by this designer Dean will lead to a decrease in the release of norepinephrine or the excitatory neurotransmitter and I'm sorry this is not a minus this is a plus design 18 is potentiating or acting as an agonist at therefore two receptor now the second way we can hyperpolarize the lower motor neuron is by giving the drug baclofen what this truck will do is act on both the gaba receptors both on the upper motor neuron and the lower motor neuron baclofen on the upper motor neuron will decrease the influx of calcium and thus will decrease the release of neurotransmitter while on the lower motor neuron gaba P will increase potassium exit leading to hyperpolarization another way is by using benzodiazepines that will act on the GABA a receptor the benzodiazepine site and causing increased chloride influx leading to hyper-polarization now we saw that all of these processes caused the lower motor neuron to hyperpolarize and thus not signals send a signal to skeletal muscles to contract the drugs that are used are benzodiazepines baclofen dis Anna Dean and gabapentin which acts by increasing gaba within the synaptic cleft now we'll see the skeletal muscle relaxants that act peripherally on the basis of their action they can be divided on those acting on the neuromuscular junctions and block those and the others which act directly on inhibiting excitation contraction coupling the skeletal muscle relaxants acting on the nmj are further divided into the depolarizing blockers the non depolarizing blockers and those which act directly on inhibiting acetylcholine release we've already studied this one but I'm just mentioning it for the sake of completeness the mechanism of action of the depolarizing blockers include two phases one is the depolarization phase which is exactly the same like acetylcholine acts on the nicotinic must muscle type of receptors on the skeletal muscle and cause contraction the second type with the second phase is that there is continuous exposure of the drug to to the receptors and thus the receptors get desensitized and do not respond to the drug anymore and thus lead to relaxation the depolarizing blockers include succinylcholine suxamethonium and deca me Tony succinylcholine is a quaternary ammonium compound and it is a synthetic one and upon administration it is degraded very quickly the nondepolarizing blockers mean that they will not depolarize the skeletal muscle but instead they will act on the nicotinic M type of receptors on the skeletal muscles and block them so acetylcholine is not able to reach them and excite them they can be divided into short acting medium acting that means intermediate acting and the long acting once the short acting ones act for about 10 to 20 minutes and include the drug neva curium which is actually the shortest acting and is rapidly metabolized by plasma colonists erases the medium acting act for about 20 to 35 minutes and include atracurium which undergo spontaneous degradation in plasma via Hoffman's degradation which is defined as the spontaneous degradation of a drug in plasma and tissue at normal body pH and temperature it also undergoes degradation by colonists races and is safe for hepatic and kidney dysfunction patients because it does not require metabolism in the liver the next intermediate acting skeletal muscle relaxant is rocuronium which has a rapid onset of action and v caronian which does not cross the placental barrier the other drugs in this category are rapper curium and Cicero curium coming to the long-acting ones they act for about greater than 35 minutes and include dtbook purine it is the natural alkaloid which is the prototype competitive blocker causing flaccid paralysis and it also causes histamine release in cases of blockade by dtbook urine we've already discussed that new segments can be used to reverse the block the next long-acting one is toxic curium which is the most potent nondepolarizing blocker remember this and it causes minimal histamine release the other long-acting ones are pancuronium and the second one I don't know how to pronounce this one another blocker that acts on the nmj by inhibiting acetylcholine release is bottle enum toxin a we've already discussed this which causes flaccid paralysis lastly we have the peripherally acting drug which directly act on inhibiting excitation contraction coupling in the skeletal muscle the chief drug is dantrolene which inhibits calcium release from the sarcoplasmic reticulum by inhibiting the ryanodine receptor channels now when the skeletal muscle is depolarized it cannot release calcium ions from the from the sarcoplasmic reticulum and the skeletal muscle does not contract dantrolene is a very important drug that is used to reverse malignant hyperthermia that can be caused by a general anesthetic such as halothane that's all about skeletal muscle relaxants