Mechanism of action of curare is -
Ans. is 'a' i.e., Reducing end plate potential o Curare (D-tubocurarine) is a competitive neuromuscular blocker.o All neuromuscular blockers bind to Nm receptors on end-plate and prevent generation of end-plate potential.Mechanism of action of muscle relaxantso To know the mechanism of action of different skeletal muscle relaxants one should know the normal sequences of events in contraction and relaxation of skeletal muscle -ContractionThere is a discharge of motor neuron.The release of Ach at the neuromuscular junction.Binding of Ach to nicotinic (NM) cholinergic receptors at end plate.Binding of Ach to nicotinic receptors causes opening of Na+ channels (NM receptor has intrinsic ion channel).Opening of Na+ channel generate end plate potential on skeletal muscle membrane.If endplate potential is above a threshold level, an action potential is generated on skeletal muscle membrane- depolarization.Depolarization of skeletal muscle membrane causes the intracellular release of Ca+2 from the sarcoplasmic reticulum.Ca+2 binds to troponin 'c', uncovering myosin binding site of actin.Cross-linking between actin and myosin, and sliding of thin filaments on thick filaments -contraction.Relaxation1Ca+2 pumped back into sarcoplasmic reticulum.2 Release of Ca+2 from Troponin.3 Cessation of interaction between actin and myosin - relaxation,o Now coming back to the mechanism of different skeletal muscle relaxants.1 Competitive (nondepolarising) blockerso The competitive blockers have affinity for Nm receptors but no intrinsic activity,o They compete with Ach for Nm receptor - called competitive blockers.o They prevent binding of Ach to Nm receptors - No opening of Na+ channels - No depolarization, so these are called non-depolarizing blockers.o Competitive blockers reduce the frequency of channel opening but not its duration or the conductance of a channel once it has opened.o When the magnitude of end plate potential falls below a critical level, it is unable to trigger propagated muscle action potential - muscle fails to contract,o Neostigmine (anticholinesterases) antagonises competitive blockers.2 Depolarizing blockerso Depolarizing blockers have affinity as well as submaximal intrinsic activity on NM receptors.o They depolarize muscle end plates by opening of Na+ channels and initially produce twitching and fasciculations (not full contraction as these drugs have submaximal activity) - o, they are called depolarizing blocker,o These drugs do not dissociate rapidly from the receptor (NM) - Persistent partial depolarization - Na+ channels get inactivated - flaccid paralysis,o Neostigmine does not antagonise depolarising blockers.o Under certain conditions depolarizing agents produce dual mechanism of neuromuscular blockade which can be divided into two phases :Phase I blockRapid in onsetThe result from persistent depolarization of muscle end plate.Has classical features of depolarization block.Block is not antagonized by anticholinesterases (neostigmine).Phase II blockSlow in onsetResults from desensitization of receptor to ACh.Resembles block produced by competitive blockers.Block is partially reversed by anticholinesterases (Neostigmine).o In man normally only phase I block is seen the typical depolarizing block.o Phase II block is seen when fluorinated anesthetics have been given or when SCh is injected in high dose.o Sch also produces phase II block in patients with atypical or deficient pseudocholinesterase.
Reducing end plate potential
Reducing presynaptic potential
Inhibits channels
Inhibits Na+ channels