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Test 2 - Dr. Selenica
PBD ANS and Cholinergic Pharm
122
Pharmacology
Professional
11/18/2011
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Term
bethanecol
 Definition
Pharmacological M-agonist bethanecol (GI and urinary tract motility)
Term
atropine
 Definition
M-antagonist atropine (dilate pupils/ increase heart rate) action
Term
Parasympathetic
 Definition
Many parasympathetic effects (incl. pupillary constriction, bronchoconstriction, and stimulation of gut and bladder motility) are caused by smooth muscle contraction.
Term
Albuterol
 Definition
(B2 agonist) dilate bronchioles selectively
Term
Metroprolol
 Definition
(B2 antagonist) selectively decrease heart rate
Term
Neostigmine
 Definition
(agonist of NMJ) increase skeletal muscle stimulation (Myasthenia gravis treatment)

SLUD (cholenergic – increase Salivation Lactation Urination Defication)
Term
Pancuronium
 Definition
(antagonist of NMJ) induces paralysis
Term
Neostigmine
 Definition
(agonist of NMJ) increase skeletal muscle stimulation (Myasthenia gravis treatment)

SLUD (cholenergic – increase Salivation Lactation Urination Defication)
Term
Pancuronium
 Definition
(antagonist of NMJ) induces paralysis
Term
Acetylcholine
 Definition
parasympathetic and somatic neuromuscular junctions.
Few sympathetic neuroeffector junctions; sweat glands and vasodilator fibers in skeletal muscle.
lack of specificity of drugs acting on acetylcholine neurotransmission
Term
Norepinephrine/ Ephinephrine
 Definition
Norepinephrine (noradrenaline) - Primary neurotransmitter at most sympathetic postganglionic neuroeffector junctions,
Epinephrine (adrenaline) is the principal catecholamine released from the adrenal medulla
Term
Other neurotransmitters
 Definition
autonomic nerves of the GI tract, genitourinary tract and certain blood vessels.
neuropeptide Y, vasoactive intestinal polypeptide, enkephalin, substance P, serotonin, adenosine triphosphate, and nitric oxide.
Term
M3 receptor
 Definition
smooth muscle contraction and gland secretion
Term
M2 receptor
 Definition
mediates cardiac slowing
Term
M1 receptor
 Definition
modulation of neurotransmission at central and peripheral sites
Term
Ach receptors action: Musacarinic Receptors
 Definition
M1-M5 human GPCR – G-Protein Coupled Receptor

Activation in skeletal muscle causes muscle contraction.
M1, M3 and M5 stimulation of PLC, IP3 and DAG
M2 and M4 inhibition AC and K+ channel activation
Hyperpolarization of the cell
Latency 100-250 ms
Term
Nicotinic receptor action
 Definition
Found in all autonomic ganglia (Nn neuron Nm muscle)
NN –Neuronal- excites neurotransmission
NM –somatic neuromuscular – excites muscle contraction
NM:5 subunits; 30-50% homology
NN: a and b subunits
Term
Nicotinic receptor structure biology
 Definition
a2 subunit - hydrophobic pocket serves as binding site for Ach agonist
Predominant ion in nAChR is Na+,
Net inward Na+ current depolarize the cell
Brief latency <10ms
Term
Choline sources
 Definition
 Synaptic Cleft
 Plasma based (lipid phosphatidylcholine)1
 Phospholipids (phosphorylcholine)
Term
Rate limiting steps of ACh: Choline uptake
 Definition
 Low affinity facilitated diffusion (Km=10-100M)
 High affinity transport (Km=1-5M) 3
Term
[image]
 Definition
[image]
Term
direct-acting acetylcholine receptor agonists
 Definition
bethanechol and pilocarpine
Term
indirect-acting acetylcholine receptor agonists
 Definition
cholinesterase inhibitors (physostigmine)
Term
nicotinic receptor antagonists
 Definition
ganglionic blocking agents (e.g., trimethaphan) and neuromuscular blocking drugs (e.g., tubocurarine).
Term
Effects of Acetylcholine of Eye iris
 Definition
contraction and miosis
Term
Effects of Acetylcholine of Salivary and lacrimal glad
 Definition
thin and watery secretions
Term
Effects of Acetylcholine of Heart
 Definition
Bradycardia
Lower conduction velocity
AV block in high doses
Slight lower in contractility
Term
botulinum toxine
 Definition
Degrades synaptobrevin and prevents the fusion of presynaptic storage vesicles with the cell membrane
Term
Catecholamines
 Definition
Norepinephrine (NE), the principal transmitter of most sympathetic postganglionic fibers
dopamine (DA), the predominant transmitter of the extrapyramidal system, mesocortical and mesolimbic neuronal pathways
epinephrine, the major hormone of the adrenal medulla
Term
α1-adrenoceptors
 Definition
mediate smooth muscle and glands contraction
Term
α2-adrenoceptors
 Definition
cause transmitter release, contraction
Term
β1-adrenoceptors
 Definition
produces cardiac stimulation
Term
β2-adrenoceptors
 Definition
mediate smooth muscle relaxation
Term
Direct- acting adrenoceptor agonists
 Definition
albuterol, epinephrine
Term
Indirect- acting adrenoceptor agonists
 Definition
Amphetamine(+), cocaine(-)
o Acts on reuptake of NE
COMT or MAO inhibitors (primarily effects on CNS )
Term
Adrenoceptor antagonists
 Definition
phentolamine, selectively blocks α-adrenoceptors;
propranolol, selective β-adrenoceptors blocker
Term
Inhibit synthesis of neurotransmitter
 Definition
Hemicholinium
Metyrosine (alpha-methyl-para-tyrosine)
Term
Prevent vesicular storage of neurotransmitter
 Definition
Vesamicol*
Reserpine
Term
Inhibit release of neurotransmitter
 Definition
Botulinum toxin
Bretylium
Term
Inhibit reuptake of neurotransmitter
 Definition
Cocaine
Term
Inhibit metabolism of neurotransmitter
 Definition
Cholinesterase inhibitors (physostigmine)
Monoamine oxidase inhibitors (phenelzine)
Term
Activate postsynaptic receptors
 Definition
• Acetylcholine, bethanechol, and pilocarpine
Albuterol, dobutamine, and epinephrine
Term
Block postsynaptic receptors
 Definition
Atropine and tubocurarine (block muscarinic and nicotinic receptors, respectively)
• Phentolamine and propranolol (block α- and β-adrenoceptors, respectively)
Term
Increase release of neurotransmitter
 Definition
Black widow spider venom (α-latrotoxin)*
Amphetamine
Term
Epinephrine/Norepinephrine
 Definition
Are released by adrenal medulla

Upon binding to B2 adrenoceptors Ep cause smooth muscle relaxation
Term
blocks the conversion of an intermediate amino acid
 Definition
Metyrosine
Term
Cerbral hemisphere
 Definition
 Cortex- site of action of many drugs
 Basal ganglia - intended actions , movement (PD)
 Limbic system: cingulate gyrus, Hippocampus, amygdala- emotions, social behaviour (AD)
Term
Felbamate
 Definition
o used in treatment of refractory epilepsy
inhibits NMDA receptors -> reduce excessive neuronal activity
Term
Dopaminergic neurons
 Definition
Subtantia niagra-control intended actions/ movements (PD –SN degeneration)
Term
Noradrenergic neurons
 Definition
Locus ceruleus- maintain vigilance, responsiveness to unexpected stimulus
COCAIN- activate this system by inhibiting reuptake of norepinephrine – Hypervigilance
TCA (antidepressant) blocks reuptake of NE
Term
Serotonergic neurons
 Definition
Brain stem (raphe nuclei) – modulating pain, regulate wakeness/ sleep
Depression- dysfunction of seretonin system
(SSRIs- used for treatment of depression)
Term
Acetylcholine
 Definition
Nucleus : Alertness/ sleep-awake cykle, AD
Term
Histamine
 Definition
Hypothalamus: forbrain arousal. Antihistamines
(H1 receptor antagonist) used to treat allergies.
Term
NITRIC OXIDE (NO):
 Definition
 Peripheral mechanism of action:
 Its released from nerves (nitrergic) innervating blood vessels and smooth muscles of the GI
 Endothelial cell–dependent mechanisms of relaxation including the coronary circulation.
 Activates specific GPCRs ->promotes NO production.
 activating GC-> cyclic GMP
 Nitrovasodilating act through conversion to or release of NO
 CNS mechanism of action:. NO is a small protein neurotransmitter
• Binds to receptors residing in the presynaptic neuron.
Term
NEUROPEPTIDES
 Definition
 Endocrine, aoutocrine and paracrine effects
 Opioids, Tachykinins, Secretins, Insulines
 Piturary hormone release : CRH, GnRH, TRH, GRH
 Opioid receptors in the spinal cord and brain mostly involved in pain sensation: Pharmacological targets of analgesics (morphine) and drug abuse (heroin)
Term
Blood Brain Barrier (BBB) permeability
 Definition
 Lipophilic substances, incl lipid soluble gases
• high w/o coefficient pass BBB
 Hydrophilic substances (glucose) pass BBB only with help of specific transporters
 Hexose transportes glucose
 3 transporters involved in the transport of amino acids (L-DOPA but not dopamine)
 Protection against toxic substances
Term
Nicotinic receptor Kinetics
 Definition
o 2 ACh molecules/ receptor= Open gate
 Resting-state channel- Low affinity for Ach
 “Desensitized” conformation – High affinity for ACh
Term
M1 ("neural")
 Definition
Autonomic ganglia, presynaptic nerve terminals, and central nervous system
Increased IP3
Modulation of neurotransmission
Term
M2 ("cardiac")
 Definition
Cardiac tissue (sinoatrial and atrioventricular nodes)
Increased potassium efflux or decreased cAMP
Slowing of heart rate and conduction
Term
M3 ("glandular")
 Definition
Smooth muscle and glands
Increased IP3
Contraction of smooth muscles and stimulation of glandular secretions
Vascular smooth muscle
Increased cGMP due to nitric oxide stimulation
Vasodilation
Term
Cholinergic Transmission: Autonomic Ganglia o nAChR
 Definition
Fast EPSP
Term
Cholinergic Transmission: Autonomic Ganglia o Dopaminergic/-adrenergic/ M2 receptors
 Definition
Slow IPSP
Term
Cholinergic Transmission: Autonomic Ganglia o M1 receptors
 Definition
Slow IPSP
Term
Cholinergic Transmission: Autonomic Ganglia o Peptide transmitters R (angiotensin, substance P)
 Definition
Late Slow IPSP
Term
CHOLINERGIC AGONIST Direct Acting
 Definition
 Achetylcholine
 Bethanechol
 Methacoline
 Pilocarpine
 Succinylcholine
 Nicotine
Term
CHOLINERGIC AGONIST Indirect Acting (reversible)
 Definition
 Edrophonium
 Neostigmine
 Physostigmine
 Pyridostigmine
Term
CHOLINERGIC AGONIST Indirect Acting (irreversible)
 Definition
 Echothiophate
 Isoflurophate
Term
CHOLINERGIC AGONIST Reactivation of Acetylcholine Esterase
 Definition
 Pralidoxime
Term
Muscarinic Receptor Agonists
 Definition
o Clinically used for diagnosis of asthma and miotics
 Charged highly hydrophilic molecules,
 Poorly adsorbed orally and low BBB penetration
 More resistant to AChE hydrolysis than Ach
o Structure variation: amphipathic vs. charged
 Tertiary amines alkaloids – high GI adsorption and CNS penetration
 Quaternary amine alkaloid (muscarine) – low bioavailability
Term
Bethanechol
 Definition
• Muscarinic
• Hypotonic neurogenic Bladder
• Urinary retention
• Intestinal atony
o Choline Esters
Term
Methacholine
 Definition
• Mainly cardivascular Muscarinic
• Brachial airway hyperreactivity
• Asthma
o Choline Esters
Term
Pilocarpine Tretiary amine
 Definition
• Muscarinic
• Glaucoma
• Miosis induction
• Xerostomia or xerophalmia
o Alkaloids
Term
pharmacology of the cholinomimetics
 Definition
o The major therapeutic uses:
 Glaucoma (closed angle and wide angle)
• Glaucoma is a disease characterized by increased intraocular pressure.
 Mechanism: Muscarinic stimulants and cholinesterase inhibitors reduce intraocular pressure by causing contraction of the ciliary body so as to facilitate outflow of aqueous humor/diminishing the rate of its secretion.
 Treatment: direct agonists (pilocarpine, emergency treatment ) or cholinesterase inhibitors (echothiophate, isoflurophate longer duration of action).
 For chronic glaucoma, these drugs have been largely replaced by topical -blockers and prostaglandin derivatives.
Term
Muscarinic Cholinergic Toxicity
 Definition
o Acute toxicity with direct –acting agents is often due to ingestion of toxic mushrooms and pilocarpine.
o Effects last 15-30 min
o Adverse effects include; nausea, vomiting, diarrhea, sweating, hypersalivation, tachycardia, bronchoconstriction
o Intoxication include treatment with competitive blockade agents- Atropine
Term
Bethanechol and Pilocarpine
 Definition
Both may increase GI motility
Term
Direct Acting Nicotinic Receptor Agonist Mechanism of action
 Definition
 Activate nicotinic receptors
 Stimulate, CNS, peripheral ganglia and NMJ: Depolarizing blocking agents
 Evoke parasympathomimetic effects in: GI, urinary system, glands
 Evoke sympathomimetic effects in: cardiovasculature, sweat glands
 Receptor desensitization occurs following long exposure
Term
Depolarizing blockade
 Definition
 Persist at the neuromuscular junction and activating the receptor continuously
 Phase 1: opening of Na+ channels and membrane depolarization: transient twitching of the muscle (Fasciculation)
 Phase 2: Membrane repolarizes but the nAchR is desensitized: prevent the opening: flaccid paralysis
Term
Succinylcholine: choline ester
 Definition
• euromuscular blocking agent
 Resistant to AchE hydrolysis
 Induces paralysis during surgery by depolarizing blockade
 Short duration of action
Term
Nicotinic Cholinergic Toxicity
 Definition
o Adverse effects of nicotine on:
 CNS overexcitation
 Skeletal muscle end-plate
 Cardiovascular system
 Treatment: antiepileptic drugs and mechanical ventilation are dictated by the symptoms.
 Atropine is used to counteract parasympathetic stimulation
Term
Continued exposure of muscle endplate to succinylcholine results
 Definition
o Repolarization
Term
AChE inhibitors
 Definition
 increasing transmission at NMJ
 increasing parasympathetic tone
 increasing central cholinergic activity
Term
 Edrophonium
 Definition
Reversible AchE inhibitors

• Absorbed poorly, destroyed by plasma esterases
• Binds to choline subsite of active center
• 5-15 min
Term
 Physostigmine
 Definition
Reversible AchE inhibitors

• Absorbed readly, destroyed by plasma esterases- enters CNS
• Binds to acyl pocket of active center
• 1-2 hr
Term
 Neostigmine
 Definition
Reversible AchE inhibitors

• Absorbed poorly, destroyed by plasma esterases- no CNS entry
• 1-2 hr
Term
 Pyridostigmine
 Definition
Reversible AchE inhibitors
• 3-6 hr
Term
 Donepezil
 Definition
Reversible AchE inhibitors

 Well absorbed, enters CNS, metabolize in liver and kidney
 60-90 hr
Term
AChE inhibitors- Myasthenia gravis
 Definition
o Myasthenia gravis is an autoimmune disease affecting skeletal muscle neuromuscular junctions.
o Mechanism: Antibodies are produced against the main immunogenic region found on nicotinic receptor-channel complex.
o Symptoms: diplopia, difficulty in speaking and swallowing, and extremity weakness. Severe disease may affect all the muscles, including those necessary for respiration.
 symptoms of excessive stimulation of muscarinic receptors (abdominal cramps, diarrhea, increased salivation, excessive bronchial secretions, miosis, bradycardia).
 Severe myasthenia (myasthenic crisis) vs. excessive drug therapy (cholinergic crisis)
o Treatment: Cholinesterase inhibitors (Edrophonium,) are extremly valuable as therapy for myasthenia. Patients having more widespread muscle weakness are also treated with immunosuppressant drugs (steroids, cyclosporine).
o Long-term therapy for myasthenia gravis is usually accomplished with pyridostigmine; neostigmine
o If muscarinic effects of such therapy are prominent, they can be controlled by the administration of antimuscarinic drugs such as atropine (develop torelance)
Term
Which of the following drug is the best drug for distinguishing between myasthenic crisis and cholinergic crisis
 Definition
Edrophonium
Term
Irreversible AchE inhibitors
 Definition
o Organophosphate compounds
o Bind covalently to AchE –long lasting effect
o Toxic and generally used as military nerve gases
 Diisopropyl fluorophosphate DFP
 Phophorylate the enzyme- extremely stabile enzyme complex
 Slow hydrolysis (< 100 hr)
Term
Reactivation of AchE
 Definition
o Pralidoxime (PAM) is pyridinium compound
o Reactivate inhibited AchE by displacing the organophosphate
o Given before aging reverse the effect of isoflurophate
o Do not enter CNS
Term
Cholinesterase Inhibitor Toxicity
 Definition
o Often due to organophosphate pesticides
o Muscarinic toxicity signs predominate: vomiting, diarrhea, profuse sweating, hypersalivation, miosis and bronchoconstriction
o Nicotinic toxicity follow after: confusion, seizure-> CNS excitation. Respiratory compromise -> depolarizing neuromuscular blockade.
o Treatment: Symptomatic treatment-> Atropine, repeated administration. Regeneration of AchE- > PAM administration
o SARIN- NERVE GAS
 Great toxic potency: 0.5 mg is lethal to adults
 Treatment: atropine, PAM
 Prophylaxis: pyridostigmine, physostigmine
Term
Antimuscarinic Agents
 Definition
CHOLINERGIC ANTAGONIST

 Atropine
 Scopolamine
 Methoscopoloamine
 Ipratropium
Term
Ganglionic Blockers
 Definition
CHOLINERGIC ANTAGONIST

 Mecamylamine
 Trimethaphan
Term
*Neuromuscular Blockers *Nondepolarizing
 Definition
CHOLINERGIC ANTAGONIST

 Tubocurare
 Pancuronium
 Vecuronium
 Rocuronium
Term
Mechanism of action and Pharmacology of CHOLINERGIC ANTAGONISTs
 Definition
o Act on Muscarinic receptors
o Evoke parasympatholytic effects
 Block of cholinergic tone-> sympathetic responses predominate
 Two classes : naturally occurring alkaloids or quaternary ammonium compounds
Term
Atropine
 Definition
 Alkaloids
 Induce myadrasis
 Reverse Bradycardia
 Irritable bowel syndrome IBS
 Organophosphate insecticide toxicity
• Antimuscarinics
Term
Scopolamine
 Definition
 Tertiary amine
 Motion Sickness
 Eliminate nausea- chemotherapy
• Antimuscarinics
Term
Methoscopolamine
 Definition
 Quaternary amine
 Low CNS penetration
 Decrease GI spasm
 Prevent bradycardia
• Antimuscarinics
Term
Ipratropium
 Definition
 Synthetic quaternary amine
 Bronchospasm prophylaxis
 Chronic obstructive pulmonary disease COPD
• Antimuscarinics
Term
Benztropine
 Definition
 Extrapyramidal symptoms
 PD
 Tremors
• Antimuscarinics
Term
Atropine toxicity
 Definition
Dose-dependent effects of atropine. Low doses of atropine inhibit salivation and sweating, and the magnitude of these effects increases as the dosage increases. Higher doses produce tachycardia, urinary retention, and central nervous system effects.
Term
Therapeutic indications for the use of antimuscarinic drugs
 Definition
o Motion sickness
o PD
o Postoperative bladder spasm
o To antidote insecticide poisoning
Term
Effect of D-tubocurarine administered previously
 Definition
 Additive
 Antagonistic
Nicotinic Receptor Antagonist
Term
Effect of decamethonium administered previously
 Definition
 No effect, or antagonistic
 Some tachyphylaxis; but may be additive
Nicotinic Receptor Antagonist
Term
Effect of anticholinesterase agents on block
 Definition
 Reversal of block
 No reversal
Nicotinic Receptor Antagonist
Term
Effect on motor end plate
 Definition
 Elevated threshold to acetylcholine; no depolarization
 Partial, persisting depolarization
Nicotinic Receptor Antagonist
Term
Initial excitatory effect on striated muscle
 Definition
 None
 Transient fasciculations
Nicotinic Receptor Antagonist
Term
Character of muscle response to indirect tetanic stimulation during partial block
 Definition
 Poorly sustained contraction
 Well-sustained contraction
Nicotinic Receptor Antagonist
Term
Exitatory AA
 Definition
E, D
Term
Inhibitary AA
 Definition
G, GABA
Term
Nicotinic Muscle type
 Definition
• Neuromuscular junctions
• Increased sodium influx
• Muscle contraction
Term
Nicotinic Ganglionic type
 Definition
• Autonomic ganglia
• Increased sodium influx
• Neuronal excitation
Term
Nicotinic CNS type
 Definition
• Central nervous system
• Increased sodium influx
• Neuronal excitation
Term
Mechanism of action Nicotinic Receptor Antagonists- Ganglionic Blockers
 Definition
Act on nicotinic receptors by blocking ion channels of the autonomic ganglia
Show no selectivity toward the parasympathetic or sympathetic ganglia
Not effective as neuromuscular antagonists
Drugs:
Trimethaphan, short term treatment of hypertension
Mecamylamine, moderate- severe hypetension, duration < 10 hr
Term
Trimethaphan
 Definition
short term treatment of hypertension
Nicotinic Receptor Antagonists- Ganglionic Blockers
Term
Mecamylamine
 Definition
moderate- severe hypetension, duration < 10 hr
Nicotinic Receptor Antagonists- Ganglionic Blockers
Term
Mechanism of action
Nicotinic Receptor Antagonists- Neuromuscular Blockers
 Definition
Nondepolarizing neuromuscular blocking drugs competitively prevent binding of Ach-> prevent depolarizing of muscle cell
Long lasting agents: tubocurare, pancuronium
Intermediate agents: vecuronium
Rapidly degraded compounds: mivacurium
Adverse effects: associated with ganglionic blockade
Histamine release
Lower blood pressure
Increase heart rate
Term
Adverse effects: associated with ganglionic blockade
 Definition
Histamine release
Lower blood pressure
Increase heart rate
Term
SUMMARY
 Definition
■ The direct-acting acetylcholine receptor agonists
include choline esters and plant alkaloids (e.g., pilocarpine). Pilocarpine is used to treat glaucoma and dry mouth.
■ The cholinesterase inhibitors indirectly activate acetylcholine receptors by increasing the synaptic concentration of acetylcholine. These drugs have both parasympathomimetic and somatic nervous system effects.
■ The reversible cholinesterase inhibitors are used to diagnose myasthenia gravis, and treat myasthenia gravis.
■ The irreversible cholinesterase inhibitors are organophosphate compounds that are widely used as pesticides and less commonly used in medical therapy.
■ Organophosphate toxicity is treated with atropine and a cholinesterase regenerator called pralidoxime.

■ The muscarinic receptor antagonists relax smooth muscle, increase heart rate and cardiac conduction, and inhibit exocrine gland secretion. They include alkaloids (e.g., atropine) and semisynthetic and synthetic drugs.
■ The muscarinic receptor blockers are used to treat bradycardia, obstructive lung diseases, intestinal spasms, and overactive urinary bladder. They are also used to reduce salivary and respiratory secretions and to produce mydriasis and cycloplegia.
■ The nicotinic receptor antagonists include ganglionic blocking and neuromuscular blocking agents (e.g., the curariform drugs, which are nondepolarizing, and succinylcholine, which is depolarizing).
■ Neuromuscular blockers are used primarily to produce muscle relaxation during anesthesia.
■ Curariform drugs competitively block nicotinic receptors in skeletal muscle. They do not cause muscle fasciculations, and their effects can be reversed by cholinesterase inhibitors.
■ Succinylcholine produces muscle fasciculations that are followed by muscle paralysis. The effects cannot be reversed by cholinesterase inhibitors.
Term
Parasympathetic
 Definition
“rest and digest” response
Innervates: pupil, chest , abdomen (heart), kidney, colon, bladder.
slows the heart rate and promotes more vegetative functions, such as digestion, defecation, and micturition.

Many parasympathetic effects (incl. pupillary constriction, bronchoconstriction, and stimulation of gut and bladder motility) are caused by smooth muscle contraction.
Term
Sympathetic
 Definition
“fight or flight” response.
Pharmacological modulators via adrenergic receptor–organ specific distribution!
Cardiovascular stimulation provides skeletal muscles with the oxygen and energy substrates required to support vigorous physical activity.
Increases in glycogenolysis and lipolysis also help provide the required energy fuels.
Adrenal medulla: contains postcynaptic neuro-endocrine cells, Synthesis of NE 80-85%
Term
Somatic Nervous System
 Definition
-The cell bodies of somatic motor neurons reside in the ventral horn of the spinal cord;
Each axon innervates a single muscle fiber, <100 muscle fibers may be supplied by one motor neuron to form a motor unit.
At NMJ, the axonal terminal loses its myelin sheath and forms the motor end plate.
 Mitochondria and synaptic vesicles are concentrated at the nerve terminal.
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