1. Acetylcholine (ACH) Acetyl-CoA + Cholin ACH +CoA
Choline-acetyl-transferase (CAT)
Acetylcholine-esterase

2. Trimethyl
Amino-
Ethanol

3. ACH synapse Presynpase acetate + choline ACH
transporter choline
Synaptic cleft ACH-esterase
Postsynapse excitatory R: Ionotropic: Nicotin R
metab.: Muscarinic R
inhibitory R: metab.: Muscarinic R

5. Postsynaptic ACH receptors
Nicotinic receptor
Ionotropic, cation (Na+) channel
Pentameric: 5 transmembrane
proteins=subunits
2 α, 1β, 1γ, 1δ
in the brain: hetero-pentameric: α2-8, β2-4
homo-pentameric: α7, 8

7. Muscarinic receptors M1 – M5
metabotropic
excitatory: slow long lasting depolarisation
due to closure of the K+ channel
M1, M3, M5
inhibitory: slow long lasting hyperpolarisation
due to opening of the K+ channel
M2, M4
ACH auto-receptors
N receptor: positive feed-back, fast onset
fast desensitization
M receptor negative feed back, slow onset
slow desensitization

8. Neuropharmacology Uni-Tuebingen
Acetylcholine Agonists
Direct Parasympathomimetics
Rezeptor Agonist
N Nicotine
M Muskarin
Pilocarpin
M, N Carbachol
Arecolin
Indirect ACH-Agonists
Indirect Parasympathomimetics
mode of action:
ACH-Esterase inhibition
reversible inhibitors:
Physostigmine
Eserine
Neostigmine
irreversible inhibitors:
Parathione
Nitrostigmine
E 605
Sarin, Tabun, Soman
ACH-Antagonists
Direct Parasympatholytics
M Belladonna Alkaloids
Scopolamine
Atropine
Pirenzepine
N Curare
Gallamin, Flaxedil
Suxamethonium
Mecamylamine, Hexamethonium
Indirect ACH-Antagonists
Indirect Parasympatholytics
Hemicholinum
Botulinus Toxin
Neuropharmacology Uni-Tuebingen

9. Cotransmitters of ACH
Cortex of the rat: Vasoactive intestinal peptide (VIP)
N. Cochlearis: Encephalin
NBM/ Septum: Substance P
ATP

11. Specific toxins for ACH neurons
AF 64: CAT inactivation
inhibits the transporter (by alcylation)
192 IgG-Saporin: Immunotoxin
antibody against p75NGF
(=low affinity NGF receptor which
is localized upon ACH neurons)

12. Anatomy of the ACH System
Periphery: Motor end plate
Vegetaive NS:
Sympathicus preganglionic: ACH - N receptor
postganglionic: Noradrenalin
Parasympath. preganglionic: ACH – N receptor
postanglionic: ACH – M receptor
Brain: –10 % are ACH ergic
Nucleus basalis whole cortex
Septum hippocampus
PPTg VTA (mesencephalon)

13. Figure: Central cholinergic pathways
Figure: Central cholinergic pathways. The six major cholinergic projection groups (sectors) are depicted (Ch1-Ch6). Therein, projections from Ch1/Ch2 and Ch4 to hippocampal, limbic and neocortical areas are implicated in learning and memory processes.

14. Physiology/Pathophysiology of ACH
Septum – hippocampus: learning, M-receptor mediated
hippocampal theta rhythm
transiently during orienting behaviour
M-receptor mediated
NBM - cortex learning N+M receptor mediated
attention
PPTg – VTA brain reward