Neuromuscular Pharmacology 59-291 Section 2, Lecture 1

Drugs change the function of Nervous System Neurotransmitters Synthesis Storage Release Inactivation Neuronal uptake Receptors Activate block

Short preganglionic Long postganglionic Thoracic/ lumbar spinal chord Discharge as a unit High post : pre fiber ratio

Long preganglionic Short postganglionic Cranial nerves +some from the sacral spinal chord Discrete activation of specific target tissues: Low post : pre fiber ratio

Sympathetic and the Parasympathetic NS have opposing effects on organ function rest & digest Fight or flight

P S

P S

Neurotransmitters and Receptors Acetylcholine (Ach)- in all autonomic parasymp. Junctions pre and post ganglionic Norepinephrine (NE)- Symp. post ganglionic neuroeffector juncion Epinephrine (E)- released from adrenal medulla in response to symp. activation Other Neurotransmitters: neuropeptide Y, vasoactive intestinal polypeptide (VIP), enkephalin, substance P, NO, seretonin, ATP

Receptors for Ach, NE, and EP Cholinergic receptors Muscarinic (M): Binds and activated by muscarine Para sympathetic neuroeffector junctions Nicotinic (N) Activated by nicotine Found in all autonomic ganglia and somatic neuromuscular junctions Adrenergic receptors Receptors for EP and NE Sympathetic neuroeffector junctions Two types: a (a1, a2 ): Mediates smooth muscle contraction b (b1 and b2): Mediates smooth muscle relaxation and cardiac stimulation

Choline acethytransferase Nerve stimulation calcium influx Removed by cholinesterase (+) Cholinesters (Direct acting) Bethanechol Pilocarpine Cholinesterase inhibitors Indirect- acting

Tyrosine hydroxylase Neuronal blocking agents block synthesis, storage and release DA:Dopamine NE: Norepinephrine MAO: Monoamine oxidase COMT: Cathecol-O-methyltransferase

Mechanism of physiological response by direct-acting sympathomimetics Mechanism of physiological response by direct-acting sympathomimetics. D, Drug; NE, norepinephrine.

Mechanism of physiological response by indirect-acting sympathomimetics. D, Drug; NE, norepinephrine.

Mechanism of physiological response by mixed-acting sympathomimetics Mechanism of physiological response by mixed-acting sympathomimetics. D, Drug; NE, norepinephrine.