Glossary of Med Chem Cholinergic Neurotransmission

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Afferent (PNS)
Efferent (PNS)
Sympathetic or Parasympathetic
pregang. neuron short, postgang. neuron long
Sympathetic or Parasympathetic
pregang. neuron long, postgang. short
endogenous chemical entities that facilitate the transmission of electrical impulses
what is the flow of a synapse?
nerve impulse --> release NT--> binds to receptor on postsynaptic neuron --> change in membrane potential
What is an ionotropic effect?
when receptor is also an ion channel binding can cause channel to change formation (immediate effect)
What is a Metabotropic effect?
when a receptor produces a second messenger (DAG, IP3)
what is the NT of all preganglionic fibers of sympathetic and p.sym division???
ACh is the NT of few postgang. fibers of parasym. division. True or False
What are the physiologic role of ACh in the CNS?
cognition, memory, behavior, coordination of movement
What are the physiologic role of ACh in the eyes?
constriction of pupil
What are the physiologic roles of ACh in the lungs and bronchioles?
increase constriction of the bronchioles and increase secretion
What are the phys roles of ACh on the GI tract?
stomach:increase contraction & secretion intestine: increase motility
What are the phys roles of ACh on the bladder
contration (micturition)
What are the phys roles of ACh on the exocrine glands?
increase secretions of salivary, sweat and lacrymal glands
What are the phys roles of Ach on the heart?
decrease rate of contraction, decrease force of contraction
What are the phys roles of ACh on the blood vessels?
relaxation of smooth muscles of blood vessels (vasodilation)
what are the 2 types of cholinergic receptors?
Nicotinic and muscarinic
what mushroom is muscarin found in?
Amanita muscarina
What two grps are contained in the structure of nicotine?
pyridine and pyrrolidine
T/F: The effect of nicotine receptors occurs w/in 0.1 to 10 msec?
How many subunits are in a glycoprotein?
What are the subunits in a glycoprotein?
2 alpha, 1beta, 1 gamma, 1 sigma
What autoimmune disease causes muscle weakness, drooping eyelids, lethargy, and possible paralysis
Myasthenia gravis
What are N1 receptors blocked by?
decamethonium, d-tubocurine, and succinylcholine
What are N2 receptors blocked by?
What type of ring does muscarine contain?
tetrahydrofuran ring
What are the three types of domains in a muscarine receptor?
seven transmembrane helical protein domain, extracellular domain, and intracellular domain.
Where are M1 receptors?
mostly in the CNS, also in the GIT
Where are M2 receptors?
mostly in the heart
Where are M3 receptors?
exocrine glands and smooth muscle
Where are M4 receptors?
tracheal smooth muscle
What conformation is ACh in at the Nicotinic receptor?
anti confromation
What conformation is ACH in at the muscarinic receptor?
gauche conformation
Agents that mimic the action of ACh at muscarinic receptors are...
cholinergic agonist
Agents that block the action of ACh at muscarinic receptors are...
cholinergic antagonist
Agents that inhibit the nicotinic-receptor mediated responses at ACh at the autonomic ganglia are...
ganglionic blockers
Agents that inhibit the nicotinic-receptor responses of ACh at teh NMJ are...
skeletal muscle relaxants
What AA can be used to synthesize ACh?
What causes the storage vesicle to fuse to pre-synaptic membrane and release ACh???
Ca 2+
What is the action of ACh?
bind to postsynaptic receptor to produce a response
What inactivates ACh?
AChE and BuChE
What blocks high affinity reuptake?
Where is BuChE found
found in plasma
The onium grp of ACh has what interaction with which AA?
ionic interaction with ASP
The ester grp of ACh has what interaction with which AA's?
H-bonbing with Thr, Asn
The ethylene grp of ACh has what interaction?
What effect does replacing the CH3 of N atom have on ACh?
it reduces the agonist activity
An alpha-alkyl grp subst. on ACh is more nicotinic or muscarinic
A beta-alkyl grp subst. on ACh is more nicotinic or muscarinic?
beta-alkyl grp subst. of ACh has what effect?
decreases the rate of hydrolysis by AChE
Why is ACh not used as a therapuetic agent?
easily hydrolyzed; poorly absorbed;readily excreted non-selective between nicotinic and muscarinic receptors
What is the brand name for methacholine chloride?
What is Provocholine used for?
diagnostic agent for bronchospasms
Although methacholine chloride is a racemic mixture, what form contains the activity?
What is the brand name for ACh?
What type of activity does Miostat have?
both muscarinic and nicotinic
What is the brand name for Carbachol Chloride?
What is Carbachol Chloride used for?
used topically for glaucoma
Is Miostat given orally?
No. it would produce widespread unwanted effects
Why is hydrolysis slower in Miostat?
it contains a Carbamyl ester
What is the brand name for Bethanechol chloride?
What is the MOA for Urecholine
stimulates cholinergic receptors in the smooth muscle of the urinary bladder and GIT
What is Bethanechol Chloride used for?
to treat or prevent post-surgical urinary retention and atony of muscles in GIT
Rank these three in order of hydrolysis (slowest to fastest) Provocholine, Urecholine, Miostat
Urecholine, Provocholine/Miostat
Rank these three in order of hydrolysis (fastest to slowest) Carbachol Chloride, Bethanechol chloride, Methacholine chloride
Methacholine/Carbachol, Bethanechol
Why does Urecholine have a decreased rate of hydrolysis
it contains both a beta-methyl grp and a carbamate
What is derived from Pilocarpus jaborandi or P. microphyllus
Pilocarpine HCl
What is the brand name for Pilocarpine HCl
What is the MOA for Pilocar
directly stimulates cholinergic receptors in the eye causing miosis, spasm of accomodation, and lowering of intraocular pressure
What % solution is Pilocarpine administered
What is the agent of choice for glaucoma treatment?
What are the systemic effects of Pilocarpine
copius sweating, salivation, and gastric secretion
Where does the aqueous humor reside?
the space between the cornea and the lens
What is the purpose of the aqueous humor?
maintains the intraocular pressure
What balances the intraocular pressure
rate of secretion, resistance to flow, resistance to resorption
What secretes the aqueous humor?
ciliary epithelial
What is the canal of schlemm?
A small opening in the anterior chamber which aqueous fluid flows through and enters venous circulation
T/F : Diabetes is a risk factor for glaucoma
What is the most common type of glaucoma?
open angle glaucoma
What causes open angle glaucoma
obstuction of trabecular mesh
What causes closed angle glaucoma?
anterior chamber becomes narrow when iris dilates which obstructs outflow of aqueous humor
What are the 2 inactive forms of pilocarpine?
Pilocarpic acid and isopilocarpine
How should pilocarpine be stored?
soln at room temp (exp 2 wks)
Where is AChE located?
NMJ and synaptic junction
What 3 AA are involved in hydrolysis of ACh
Ser, His, Glu
What is more stable the acetylated enzyme or the acylated enzyme?
How do Reversible inhibitors of AChE work?
react with enzyme to form an acylated enzyme or bind to enzyme with greater affinity than ACh
What is the brand name for physostigmine?
What is the MOA of Eserine?
inhibits AChE
What is the kinetic potent range of a drug
the nanomolar range
What is physostigmine used for?
tmt of glaucoma; tmt of overdoses of anticholinergics; investigational Alzheimers
T/F: A monosubstituted carbamate will carbamate an enzyme faster then a disubstituted carbamate?
In solution, physostigmine is hydrolyzed to what?
eseroline and carbamic acid
What is the brand name neostigmine bromide?
What is the location of the dimethylcarbamate grp compared to the trimethylammonium on Prostigmin?
Which is more active in an acidic pH Neostigmine or physostigmine bromide
What is Prostigmin used for?
to prevent post-surgical atony of muscles; treat glaucoma; myasthenia gravis
What are some symptoms of Myasthenia Gravis?
diplopia, weakness of jaw, weakness of proximal muscles
What is the brand name for pyridostigmine bromide?
What is the Mestinon used for?
tmt of myasthenia gravis
What is the brand name for Edrophonium Chloride?
What is Tensilon used for?
a diagnostic agent
How is Edrophonium Chloride used in the emergency room?
as a reversal of curare overdose
what is the MOA for Tensilon?
competes with ACh for binding to AChE
How is Edrophonium chloride administered
IM and IV
What is the pharmacological challenge with with Tensilon
it has a transitory but dramatic improvement in muscle function
what is the brand name for ambenonium chloride
What is Mytelase used for?
tmt of myasthenia gravis for patients that don't respond to neostigmin or pyridostigmine
What is Ambenonium chloride derived from?
oxalic acid
What is the MOA for Mytelase?
competes with ACh for enzyme AChE
What is the brand name for Demecarium Bromide
Is Humorsol hydrophilic or lipophilic
What is Demecarium bromide used for
the tmt of wide angle glaucoma
What is the DOA for Humorsol
about 2 days
How is Demecarium bromide administered
topically because it is very potent
What is the brand name for Tacrine HCl
Which drug has a tetrahydroacridine ring
Cognex/ Tacrine HCl
What is the MOA of Tacrine HCl?
centrally-acting AChE inhibitor
What is Cognex used for?
first drug approved for tmt of Alzheimers
Why is there limited use for Cognex?
it is hepatotoxic
What is the brand name for Donepezil HCl?
What is Aricept used for?
tmt of Alzheimers and dementia
What is the MOA for Donepezil HCl
centrally acting reversible inhibitor of AChE
What enzyme is Aricept selective for?
T/F : Aricept has a greater affinity for AChE in the periphery then the brain?
What % of the 6-desmethyldonapezil metabolite is active?
What is the brand name for Rivastigmine
What is the MOA of Exelon?
centrally acting AChEI
What is the DOA for Rivastigmine
10 hours
What is Exelon used for?
tmt of Alzheimers
What is the active ingredient in Turmeric?
What is the MOA for organophosphates?
permits the accumulation of ACh at nerve endings and produce an exacerbation of ACh like actions
What are the 3 characteristics of Organophosphates
very lipophilic, high vapor pressure and very low therapeutic index
What are the four functional grps that make up an organophosphate?
O,S; alkoxy; alkoxy/alkyl/tertamine; good leaving grp
How do you calculate Therapeutic Index
lethal dose / effective dose
T/F : Phosphorylated enzymes are very stable to hydrolysis
When does aging occur?
when a phosphoester bond is cleaved
What is the brand name for Isofluorphate?
What is Floropryl used for?
tmt of glaucoma
T/F : Floropryl is very toxic
What effect does Isofluorophate have on the eye?
It reduces the intraocular pressure
What is the DOA for Floropryl
4 weeks
What serious side effect can occur if solution of Floropryl is not dilute?
detachment of Retina
What is the brand name for Echothiophate Iodide?
Phospholine Iodide
What is Phospholine Iodide used for?
tmt of glaucoma
How is the therapeutic window determined?
What is Sarin used for?
chemical warfare (nerve gas)
What are Paraoxon and Parathion used for?
agricultural insecticides
What effects does Sarin have on Humans?
depression of respiratory rate, bradycardia, hypothermia, hypotension
What is the brand name for Pralidoxime chloride
What is Pralidoxime chloride also known as?
WHat does hydroxylamine do?
can cleave a phosphate ester
When is 2-PAM effective
w/in 36-48 hours of poisoning
Why is 2-PAM ineffective after 48hours of the poisoning
the enzyme will start aging
What is a compound with affinity for the receptor but lacks intrinsic activity
cholinergic Antagonist
What are the 2 subgroups for Nicotinic Antagonists?
ganglionic blockers and neuromuscular blocking agents
Where is the site of action for cholinergic antagonists in the autonomic division in the sympathetic nervous system
at the ganglia
Where is the site of action for cholinergic antagonists in the somatic division?
and the NMJ
What are the 7 other terms for Muscarinic antagonists?
antimuscarinics; anti cholinergics; cholinergic antagonist; cholinergic blockers; parasympatholytics; parasympathatics;postganglionic blocking agents; anti spasmodics
What effect does antimuscarinics have on the heart
produces tachycardia
What effect does antimuscarinics have on the lungs
dialation of bronchioles
What effect does antimuscarinics have on the GIT
decrease secretion and decrease motility
What effect does antimuscarinics have on the bladder?
urinary retention
what effect does antimuscarinics have on the eyes
mydriasis and cycloplegia
what effect does antimuscarinics have on the skeletal muscle
what effect does antimuscarinics have on the CNS
stimulation or depression
What effect does antimuscarinics have on the mucous membrane?
decrease salivation and decrease perspiration
define mydriasis
dialation of pupil
Define cycloplegia
temporary paralysis of ciliary muscle
Define sialorrhea
Define hyperhydrosis
exsessive sweating
What is the clinical significance of antimuscarinics?
increase cardiac output; antispasmodic effect, antisecretory effect; mydriatic and cycloplegia effects; Parkinson's disease; asthma; cholinergic poisoning; antisialoqoque; antihydrotic
What are the most common side effectts of anticholinergics?
dry mouth, mydriasis, urinary retention
What condition does mydriasis precipitate?
What is BPH?
benign prostratic hyperplasia -> increased cell # of normal prostratic cell
Where is Atropine and Scopolamine found?
Atropa Belladona, Hyoscymus niger, Datura Stramonium
Give examples of Solanaceous alkaloids?
atropine, scopalamine, homatropine, ipratropium
What ring in in Atropine
What position must the 3alpha-hydroxy grp be in for activity (for atropine)
What makes up a tropane ring?
piperidine, pyrrolidine
What neurotropic effect does atropine have?
interfers w/ nerve impulse transmission
What musculotropic effect does Atropine have?
produced by direct depression of smooth muscle of GIT
What is the AOC for the musculotropic effect of Atropine
What is Atropine sulfate used for?
primarily mydriatic during refraction studies
What other effects does Atropine sulfate have?
tachycardia, constipation, xerostomia, dry eyes, CNS stimulation, decrease secretion in GIT
What are the contraindications of Atropine sulfate?
open angle glaucoma, BPH, severe hypertension
What is another name for Scopalamine?
What is Scopalamine used for?
motion sickness
What are the other effects of Hyoscine?
sedation, and dry mouth
T/F: Homatropine HBr is twice as potent as atropine
False. it is 1/2
What structures make up Homatropine HBr?
tropine and Mandelic acid
What is Homatropine HBr used for?
primary for mydriatic and cycloplegic properties
What is the brand name for Ipratropium Bromide
What is the MOA for Atrovent
produces bronchodialation by competitive inhibition of cholinergic receptors bound to smooth muscles of bronchioles
What is Atrovent used for?
used to treat asthma and COPD
What is the brand name for Clindinium Bromide?
Which muscarinic receptors does Quarzan have a high affinity for?
M1 and M3
What is Quarzan used for?
antispasmodic and antisecretory effects
What drug is Quarzan combined w/ for peptic ulcers?
What is the brand name for Clindinium Br and Chlordiazepoxide?
What is the brand name for Dicyclomine HCl?
What is Bentyl used for?
spasmolytic effect on smooth muscle of GIT
T/F: Bentyl has 1/8 neurotropic activity of Atropine and 2x musculotropic activity
What drug is used to treat IBS?
Dicyclomine HCl
What is the brand name for Glycopyrrolate?
What is Robinul used for?
spasmolytic and antisecretory effect
What muscarinic receptor does Robinul have a high affinity for
What effect does Glycopyrrolate have if given in high doses
can block ganglionic and NMJ receptors
What is the brand name for propantheline Bromide?
T/F: Pro-Banthine is 1/2x potent as Banthine.
False. it is 2-5x more potent
What is Pro-Banthine used for?
antispasmodic and antisecretory effects
what disease are aminoalcohol ethers and aminoalcohols primarily used to manage
What are the four primary symptoms of PD?
fine tremors; rigidity or stiffness of limbs; slowness of movement; postural instability
What are some other symptoms of PD
oculogyric crisis; mask face; drooling; depression
What part of the brain is responsible for producing dopamine?
the substantia nigra
Is the pyrimidal tract inhibitory or excitatory?
Is the extrapyrimidal tract excitatory or inhibitory?
Dopamine is an excitatory or inhibitory NT?
What is different in the brain of a PD patient?
The substantia nigra are dead
What are the characteristics of primary PD?
idiopathic; incurable; tmt is palliative
What are two infectious causes of secondary PD
encephalitis and syphilis
What drugs can induce secondary PD?
reserpine, haloperidol, and chlorpromezine
What class of drugs are used to treat PD
Dopaminergic agonist
What is the brand name for Diphenhydramine?
What are some side effects of Benadryl?
drowsiness, CNS depression
What is the brand name for Benztropine mesylate?
What patients are Cogentin targeted for?
useful in patients that can't tolerate central excitation
What patients should you take caution with when using Cogentin?
patients with glaucoma and BPH
What is the brand name for Biperiden?
What is Akinetin used for?
useful for tmt of PD and also in a variety of spastic disorders
What effects does Biperiden have on patients?
alleviates akinesia, rigidity and tremors
What is the brand name for Procyclindine HCl?
What is Kemadrin used for?
tmt of PD
what structural ring does Kemadrin contain?
a pyrrolidine ring
What is the brand name for Trihexyphenidyl HCl?
What is Artane used for?
tmt of PD
What structural ring does Artane have?
piperidine ring

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