Antagonists of the Muscarinic Cholinergic Receptor

“cholinergic blocking agents.”

Drugs that inhibit the interactions of ACh or

acetylcholine with its receptor are called

Antagonist

it has the affinity but has NO INTRINDIC ACTIVITY

- will block the receptor = ACh cannot bind to its receptor =

prevents/ affects neurotransmissions

Agonist

with affinity and intrinsic activity

QUATERNARY NITROGEN & TERTIARY NITROGEN

IMPORTANT STRUCTURES OF ANTAGONIST

Essential to the structure

- Reduces passage across the blood-brain

barrier

IMPORTANT STRUCTURES OF ANTAGONIST

QUATERNARY NITROGEN

For broader volume of distribution (Increase

lipophilicity)

IMPORTANT STRUCTURES OF ANTAGONIST

TERTIARY NITROGEN

atropine

Naturally occurring alkaloid

will decrease the action but

the reduction on muscarinic effect will be greater

Alteration in alpha carbon

beta-carbon

Greater reduction in nicotinic activity is due to…substitution happens in ethylene bridge

Atropa belladonna

Atropine from

± or dl Hyoscyamine

ATROPINE aka

Scopolamine

HYOSCINE AKA:

Non- depolarizing/ Competitive Agents

Depolarizing Agents

NEUROMUSCULAR BLOCKING AGENTS 2 types

Depolarizing Agents

Flexible structures with free bond

rotation. They were devised (not

natural products) through mimicry of

the N+ - N+ distance, but they act by a

different mechanism

Curare

natural (+) tubocurarine

Tetrahydroisoquinoline & CPPP Nucleus

Synthetic compounds

Succinylcholine

2 moles of acetylcholine, longer compared to

the degradation of acetylcholine

SUCCINYLCHOLINE

Substrate for acetylcholinesterase

● Onset- 30s; duration- 5-10 min

SUXAMETHONIUM

The ester groups are susceptible to chemical and

enzymatic hydrolysis but have a longer effect than

acetylcholine

● Once hydrolysis occurs, the molecule can no longer bridge

the two receptor sites and becomes inactive

DECAMETHONIUM

Simple analog of tubocurarine

Curare

NICOTINIC ANTAGONISTS

Chondrodendron tomentosum

A poison from a plant called …and caused paralysis as well as stopping the

heart

Tubocurarine

An antagonist of acetylcholine which blocks nerve

transmissions from nerve to muscle e Competitive agents

are usually bulky rigid molecules with an optimum

distance of 10 +/ -0.1A

Tubocurarine

Slow onset (>5 min) long duration of action (30 mins)

Tubocurarine

Curare alkaloid

Pancuronium and Vecuronium

Act like tubocurarine, but with a steroid nucleus acting as

the spacer. The distance between the quaternary

nitrogens is 1.1 nm as compared to 1.4 nm in

tubocurarine

Acyl groups

Pancuronium and Vecuronium

were also added to introduce two

acetylcholine esters into the molecule in order to improve

affinity for the receptor sites. Contain CPPP nucleus

Snake toxins

Bind irreversibly to the acetylcholine, thus blocking

cholinergic transmissions

Alpha bungarotoxin- Bungarus multicinctus

Snake toxins

Bungarus multicinctus

Snake