Cholinoceptors

Two classes of receptors for ACh are recognised-muscarinic and nicotinic; the former is a G
protein coupled receptor, while the latter is a ligand gated cation channel.
Muscarinic These receptors are selectively stimulated by muscarine and blocked by
atropine. They are located primarily on autonomic effector cells in heart, blood vessels,
eye, smooth muscles and glands of gastrointestinal, respiratory and urinary tracts, sweat
glands, etc. and in the CNS. Subsidiary muscarinic receptors are also present in autonomic
ganglia where they appear to play a modulatory role by inducing a long-lasting late EPSP.

Nicotinic These receptors are selectively activated by nicotine and blocked by
tubocurarine or hexamethonium
NM: These are present at skeletal muscle end plate:are selectively stimulated by phenyl
trimethyl ammonium (PTMA) and blocked by tubocurarine. They mediate skeletal
muscle contraction.
NN: These are present on ganglionic cells (sympathetic as well as parasympathetic),
adrenal medullary cells (embryologically derived from the same site as ganglionic cells)
and in spinal cord and certain areas of brain. They are selectively stimulated by dimethyl
phenyl piperazinium (DMPP), blocked by hexamethonium, and constitute the primary
pathway of transmission in ganglia.

CHOLINERGIC AGONISTS
Choline ester
1. Acetylcholine
2. Methacholine
3. Carbachol
4. Bethanechol

Alkaloids
1. Muscarine
2. Pilocarpine
3. Arecoline

CHOLINERGIC DRUGS
(Cholinomimetic, Parasympathomimetic)
These are drugs which produce actions similar to that of ACh, either by directly interacting
with cholinergic receptors (cholinergic agonists) or by increasing availability of ACh at
these sites (anticholinesterases).

ANTICHOLINESTERASES
Anticholinesterases (anti-ChEs) are agents which inhibit ChE, protect ACh from hydrolysis-
produce cholinergic effects in vivo and potentiate Ach both in vivo and in vitro. Some anti
ChEs have additional direct action on cholinergic receptors.

Reversible
Carbamates
1. Physostigmine (Eserine)
2. Neostigmine
3. Pyridostigmine
4. Edrophonium
5. Rivastigmine, Donepezil
6. Galantamine
Acridine
1. Tacrine

Irreversible
Organophosphates
1. Dyflos (DFP)
2. Echothiophate
3. Parathion*, Malathion*
4. Diazinon* (TIK-20)
5. Tabun, Sarin, Soman
Carbamates
1. Carbaryl* (SEVIN)
2. Propoxur* (BAYGON)
Myasthenia gravis: Myasthenia gravis is an autoimmune disorder affecting about 1 in
10,000 population, due to development of antibodies directed to nicotinic receptor at the
muscle endplate neostigmine, Pyridostigmine
atropine can be added to block them.
Myasthenic crisis is characterized by acute weakness of respiratory muscles.

ANTICHOLINERGIC DRUGS
(Muscarinic receptor antagonists, Atropinic, Parasympathoiytic)
Conventionally, anticholinergic drugs are those which block actions of ACh on autonomic
effectors and in the CNS exerted through muscarinic receptors. Though nicotinic
antagonists also block certain actions of ACh, they are generally referred to as 'ganglion
blockers' and 'neuromuscular blockers'.
Atropine, the prototype drug of this class, is highly selective for muscarinic receptors, but
some of its synthetic substitutes do possess significant nicotinic blocking property in
addition. The selective action of atropine can easily be demonstrated on a piece of guinea
pig ileum where
ACh induced contractions are blocked without affecting those evoked by histamine, S-HT or
other spasmogens. The selectivity is, however, lost at very high doses. All anticholinergics
are competitive antagonists.

CLASSIFICATION
1 . Natural alkaloids Atropine, Hyoscine (Scopolamine).
2. Semisynthetic derivatives Homatropine, Atropine methonitrate, Hyoscine butyl
bromide, Ipratropium bromide, Tiotropine bromide.
3. Synthetic compounds
(a) Mydriatics: Cyclopentolate, Tropicamide
(b) Antisecretory-antispasmodics:
(i) Quaternary compounds: Propantheline, Oxyphenonium, Clidiniurn, Pipenzolane
methylbromide, Isopropamide,
(ii) Tertiary amines: Dicyclomine, Valethamane, Pirenzepine.
(c) Vasicoselective: Oxybutynin, Flavoxate, Tolterodine.
(d) Antiparkinsonian: Trihexyphenidyl, Procyclidine, Biperiden.

DRUGS ACTING ON AUTONOMIC GANGLIA
Ganglionic stimulants
Selective nicotinic ag01zists
1. Nicotine (small dose)
2. Lobeline
3. Dimethyl phenyl
4. piperazinium (DMPP)
5. iodide
6. Tetramethyl ammonium (TMA)
Nonselective/nwscaranic agonists
1. Acetylcholine
2. Carbachol
3. Pilocarpine
4. Anticholinesterases
5. MCN 343-A

Ganglion blocking agents
A. Competitive blockers
1. Quaternary ammonium compounds Hexamethonium, Pentolinium
2. Amines (secondary/tertiary) Mecamylamine, Pempidine
3. Monosulfonium compound Trimethaphan camforsulfonate

B . Persistent depolarising blockers
1. Nicotine (large dose)
2. Anticholinesterases (large dose)

ADRENERGIC TRANSMISSION
Adrenergic (more precisely 'Noradrenergic') transmission is restricted to the sympathetic
division of the ANS. There are three closely related endogenous catecholamines (CAs).
Noradrenaline (NA) It acts as transmitter at postganglionic sympathetic sites (except
sweat glands, hair follicles and some vasodilator fibres) and in certain areas of brain.
Adrenaline (Adr) It is secreted by adrenal medulla and may have a transmitter role in the
brain.
Dopamine (DA) It is a major transmitter in basal ganglia, limbic system, CTZ, anterior
pituitary, etc. and in a limited manner in the periphery.

THERAPEUTIC CLASSI FICATION OF ADREN ERGIC D RUGS

I . Pressor agents
1. Noradrenaline
2. Phenylephrine
3. Ephedrine
4. Methoxamine
5. Dopamine
6. Mephentermine

I I . Cardiac stimulants
1. Adrenaline
2. Isoprenaline

I l l . Bronchodilators
1. Isoprenaline
2. Salbutamol (Albuterol)
3. Terbutaline
4. Dobutamine
5. Salmeterol
6. Formoterol
7. Bambuterol

I V . Nasal decongestants
1. Phenylephrine
2. Naphazoline
3. Xylometazoline
4. Pseudoephedrine
5. Oxymetazoline
6. Phenyl propanolamine

V . CNS stimulants
1. Amphetamine
2. Methamphetamine
3. Dexamphetamine

V I . Anorectics
1. Fenfluramine
2. Sibutramine
3. Dexfenfluramine

V I I . Uterine relaxant and vasodilators
1. Ritodrine
2. Salbutamol
3. Isoxsuprine
4. Terbutaline

ADRENERGIC BLOCKING DRUGS
These drugs inhibit adrenergic responses mediated through the adrenergic receptors
without affecting those mediated through receptors.

CLAS S I F I CATION:
L Nonequilibrium type
( i) -Haloalky lam ines-Phenoxybenzamine.

I I . Equilibrium type (competitive)
A . Nonselective
(i) Ergot alkaloids-Ergotamine, Ergotoxine
(ii) Hydrogenated ergot alkaloids-Dihydroergotamine (DHE), Dihydroergotoxine
(iii) Imidazolines-Tolazoline, Phentolamine
(iv) Miscellaneous-Chlorpromazine
B . 1 selective-Prazosin, Terazosin, Doxazosin, Tamsulosin
C. 2 selective-Yohimbine