Why Study the Autonomic Nervous System?

1. Path physiology Medicinal Chemistry Why Study the Autonomic Nervous System? ANS Therapeutics Pharmacology PREPARED BY ANIRUDH JOSHI ASST PROFFESOR BRNCOP MANDSAUR Disease State Management

2. Organization of The Nervous System Central Nervous System Peripheral Nervous System Autonomic Nervous System Sympathetic Parasympathetic

3. How do we define neuron types in the ANS? • ANS Parasympathetic Sympathetic Acetylcholine Norepinephrine (Noradrenaline) Muscarine Epinephrine (Adrenaline) Nicotine

4. a b a Parasympathetic Ganglionic Synapse • ANS Acetylcholinesterase Ca2+ Na+ ACH Action Potential Nicotinic Receptor Na+ Preganglionic neuron

5. Na+ Sympathetic Organ Synapse • ANS Sympathetic Organ Synapse Ca2+ G NE Action Potential Postganglionic neuron

6. Summary of sympathetic neurons and synapses Preganglionic neurons • Short • Synapse with postganglionic neurons near spinal cord • Release acetylcholine (ACH) to activate nicotinic receptors on postganglionic neurons Postganglionic neurons • Long • Synapse on the target organ • Release norepinephrine to activate adrenergic receptors on target organs

7. Exceptions in the sympathetic nervous system: • Sweat glands: • Postganglionic neurons involved with stress-related excretion release norepinephrine (“sweaty palms”) • Postganglionic neurons involved with thermoregulation release acetylcholine

8. Exceptions in the sympathetic nervous system • Kidneys: • Postganglionic neurons to the smooth muscle of the renal vascular bed release dopamine • Adrenal gland: • Preganglionic neurons do not synapse in the paraverterbral sympathetic ganglion • Preganglionic neurons synapse directly on the adrenal gland, release acetylcholine, and activate nicotinic receptors on the adrenal gland • Adrenal glands release epinephrine into systemic circulation Most postganglionic sympathetic neurons release what neurotransmitter?

9. How do drugs influence the ANS? • Mimic or block the effects of the two primary neurotransmitters, Acetylcholine and Norepinephrine/Epinephrine • Drugs that mimic neurotransmitters are referred to as “receptor agonists” • These drugs activate receptors • Drugs that block neurotransmitters are referred to as “receptor antagonists” • These drugs block the endogenous neurotransmitters from activating receptors

10. Classification of drugs affecting the ANS • Parasympathetic nervous system Mimic acetylcholine = cholinergic = muscarinic agonists = parasympathomimetic Block acetylcholine = anticholinergic = muscarinic antagonist = parasympatholytic • Sympathetic nervous system Mimic norepinephrine = adrenergic = adrenergic agonist = sympathomimetic Block norepinephrine = antiadrenergic = adrenergic antagonist = sympatholytic

11. SYNAPSES AND DRUGS PREPARED BY ANIRUDH JOSHI ASST PROFFESOR BRNCOP MANDSAUR

12. What is a synapse? • A synapse is the junction between 2 neurones. • There is a very narrow gap of about 20nm between neurones called the synaptic cleft. • An action potential cannot cross the synaptic cleft, so nerve impulses are carried by chemicals called neurotransmitters.

13. A Synapse • Pre-synaptic neurone = neurone sending impulse • Post-synaptic neurone = neurone receiving impulse

14. Neurotransmitter • Neurotransmitter is made by the pre-synaptic neurone and is stored in synaptic vessels at the end of the axon. • The membrane of the post-synaptic neurone has chemical-gated ion channels called neuroreceptors. These have specific binding sites for neurotransmitters.

15. Cholinergic Synapses • This is an electron micrograph of synapses between nerve fibres and a neurone cell body. • Acetylcholine is a common transmitter. • Synapses that have acetylcholine transmitter are called cholinergic synapses. • Some neurones form more than 1 synapse.

16. What happens at a cholinergic synapse? Stage 1 • An action potential arrives at presynaptic membrane. Voltage gated calcium channels in the presynaptic membrane open, calcium ions enter the presynaptic neurone.

17. What happens at a cholinergic synapse? Stage 2 • Calcium ions cause synaptic vesicles to fuse with the presynaptic membrane, releasing acetylcholine into the synaptic cleft.

18. What happens at a cholinergic synapse? Stage 3 • Acetylcholine diffuses cross the synaptic cleft and binds to specific neuroreceptor sites in the post synaptic membrane.

19. What happens at a cholinergic synapse? Stage 4 • Sodium channels open. Sodium ions diffuse into the postsynaptic membrane causing depolarisation, which may initiate an action potential.

20. What happens at a cholinergic synapse? Stage 5 • Acetylcholinesterase breaks down acetylcholine. The products diffuse back into the presynaptic neurone where acetycholine is resynthesised using ATP from the mitochondria.

21. Neuromuscular Junctions • Same stages as cholinergic synapses, but in this case the postsynaptic membrane is the muscle fibre membrane, (Sarcolemma). Depolarisation of the sarcolemma leads to contraction of muscle fibre.

22. Drugs • Drugs which have molecules of similar shape to transmitter substances can affect protein receptors in postsynaptic membranes. • Drugs that stimulate a nervous system are called AGONISTS • Drugs that inhibit a nervous system are called ANTAGONISTS.

23. DRUG ACTION EFFECT Mimic a neurotransmitter Switch on a synapse Stimulate the release of a neurotransmitter Switch on a synapse Open a neuroreceptor channel Switch on a synapse Block a neuroreceptor channel Switch off a synapse Inhibit the breakdown enzyme Switch on a synapse Inhibit the Na+K+ATPase pump Stop action potentials Block the Na+ or K+ channels Stop action potentials Various effects of drugs on synapses:

24. Effect of nicotine and atropine

25. Summary • A synapse is the point where 2 nerve cells meet. Tiny gap = synaptic cleft. • Chemical transmitter released from presynaptic neurone diffuses across synaptic cleft & fits into receptors on postsynaptic membrane. May cause postsynaptic neurone to depolarise & set up action potential. • Neuromuscular junction = motor neurone connects with muscle fibre – similar to a synapse. • Many drugs affect synapses.