Curare alkaloids- Neuromuscular Blocking Drugs. Introduction. Types of Neuromuscular Blocking Drugs. Mechanism of action. Chemistry of Curare alkaloids. Structure-activity relationships. Synthetic analogs of curarine. Therapeutic uses.

1. NEUROMUSCULAR BLOCKING DRUGS
CURARE ALKALOIDS
NURI FARZINA RAHMAN
M. PHARM
(PHARMACEUTICAL CHEMISTRY)

2. NEUROMUSCULAR BLOCKING DRUGS
•Neuromuscular blocking agents are primarily
used in conjunction with general anesthetics to
provide muscle relaxation for surgery.
•These are the drugs that prevent interaction of
acetylcholine at nicotinic receptor at
neuromuscular junction.
TYPES OF NEUROMUSCULAR BLOCKING
AGENTS:
The neuromuscular blocking agents are divided
into two categories, namely :
a. Non-depolarizing Neuromuscular Blocking
Drugs (Examples :Tubocurarine chloride ;
Metocurine iodide ; Gallamine triethiodide ;
Hexafluoronium bromide ; etc.)
b. Depolarizing Neuromuscular Blocking
Drugs (Examples : Suxamethonium chloride ;
Suxethonium bromide ; Decamethonium
bromide)

3. NEUROMUSCULAR BLOCKING DRUGS
CURARE TYPE NEUROMUSCULAR DRUGS
→Curare-type drugs essentially contain a bulky
structure together with a minimum of one quaternary
ammonium group.
→These are obtained from bark and stem of
Strychnos castelnoci and Strychnos toxifera.
→Initially, South Americans and Indians used curare
as a very potent arrow poison.
Fig: Gallamine triethiodide Fig: Tubocurarine chloride

4. NEUROMUSCULAR BLOCKING DRUGS
MECHANISM OF ACTION OF CURARE TYPE
DRUGS:
•Curare drugs are primarily used as adjuvants in
surgical anesthesia to obtain relaxation of skeletal
muscles.
•These drugs exert their action by making the
motor end-plate membrane of the myo-neural
junction incapable of reacting to acetylcholine,
which functions as the neuro-transmitter.
•Curare drugs are non-depolarizing and
competitive inhibitor of acetylcholine (Ach) at
neuromuscular junctions preventing the binding of
Ach to their Nicotinic Ach receptor.
•These post-synaptic receptors are responsible
for generating action potentials resulting in
muscle contraction.
•Thus, binding of the curare prevents action
potentials from occurring at the post-synaptic
membrane and as a result, leads to paralysis of
voluntary muscle groups.

5. CHEMISTRY OF CURARE DRUGS
•The active ingredient in crude curare is D-
tubocurarine.
•Curare is an organic compound classified as either
an isoquinoline or indole alkaloid. In other words,
they are aromatic, nitrogen-containing compounds.
•They do not cross the blood-brain-barrier due
to the presence of two quaternary nitrogen.
•Presence of these quaternary nitrogen groups
makes the compound highly polar.
•Tubocurarine and C toxiferine consist of a cyclic
system with quaternary ammonium ions.
•On the other hand, while acetylcholine does not
contain a cyclic system, it does contain a
quaternary ammonium ion.
•Because of this shared moiety, curare alkaloids
can bind readily to the active site of receptors for
acetylcholine (ACh) at the neuromuscular junction,
blocking nerve impulses from being sent to the
skeletal muscles, effectively paralyzing the muscles
of the body.

6. SAR OF CURARE DRUGS
FIG: D-tubocurarine.

8. THERAPEUTIC USES OF CURARE DRUGS
•Curare was discovered in South America and was first
used in poison arrows for hunting.
•In medicine, curare has been used as a treatment for
tetanus and strychnine poisoning
•It has been used as a paralyzing agent for
surgical procedures.
•During 1857 to 1867 curare was used in the treatment
of convulsive conditions, such as epilepsy, rabies, etc.
•Curare has been used in the treatment of
hydrophobia.
Fig: Historical Use Of Curare Blow
Darts