1. Parasympathetic Postganglionic
Blocking Agents
- Antimuscarinic
Anticholinergic
Parasympatholytic
Cholinolytic

2. Antimusarinic- acts by competitive antagonism of Ach binding to muscarinic
receptor
Therapeutic actions:
3 predictable and clinically useful results from blocking the muscarinic effetcs of Ach:
1. Mydriatic effect and Cyclopegia
Beneficial in :
•opthalmology
•Principal use in refraction studies in fitting lenses
•Used to treat inflammation of the cornea (keratitis)
•Treat inflammed iris and ciliary organs
2. Antispasmodic effect
3. Antisecretory effect
Anticholinergic
Therapeutic actions:
•Minor role in management of peptic ulcer
•Treatment for parkinsonism by decreasing the activity of cholinergic neurons in basal
ganglia.
Parasympatholytic
Cholonolytic drugs

3. Solanaceous Alkaloids and Analogs
Forerunners of the class of antimusarinic drugs:
•(-)-hyoscyamine, atropine
•Scopolamine (hyoscine)
Found in :
1. Henbane (Hyoscyamus niger)
2. Deadly nightshdae (atropa belladona)
3.Jimsun weed (Datura stramonium)

4. •used topically for analgesic effect on
hemorrhoids, skin infectinon, various itching
dermatoses.
•Application of belladona and its alkaloids
results in mydriasis.
•causes dimution of secreation
•Increase heart rate
•Depress motility of GI tract
•Acts as antispasmodic on various smooth
muscles
•Directly stimulates the respiratory center

5. Products of Solanaeous Alkaloids and Analogs :
1. Atopine, USP
• Standard by which similar drug are measured.
•Widely used antispasmodic. A depressant effect on parasympathetically innervated
smooth muscles.
•Blocks all muscarinic receptor subtypes
•Tropine ester of racemic tropic acid and is optically inactive
•Occurs naturally in various Solanacea
•Obtain from conventional method of alkoloid isolation from plant material (crude
mixture of atropine) then racemized to atropine by refluxing chloroform or treating
with cold dilute alkali.
•Optically inactive, white, odorless crystals possesing bitter taste.
•Not very soluble in water but more soluble in alcohol
•Soluble in glycerin, ether and chloroform.
•Free base is useful when nonaqeus solutions are to be made (e.i ointment base)
•Plasma half life about 2-3 hours
•metabolized in liver to become tropic acid and tropine.

6. 2. Atropine sulfate, USP. (Atropisol)
•prepared by neutralizing atropine acetone or ether solution w/ alcoholic
solution of sulfuric acid with care , to prevent hyrdolysis.
•Colorless crystals or white crystalline powder.
•Efflorescent in dry air and should be prevented from light.
•Free soluble in water and in glycerin
•Aqeous solution are not very stable, although it can be sterilized at 120C in
autoclave if pH is kept below 6.
•Produces mydriatic effect ( used 0.5%-1% solutions or gelatin disk)
•Administerd in small doses before anesthesia.
•Atropine causes restlesness, prolonged pupillary dilation, loss of visual
accomodation and give rise to arrythmias.
•Used as anesthetic premedicant to reduce excesive salivary and airway
secreations and prevent vagal reflexes.
•Used in rhinitis tablets for relief of colds
•In cathartic preparations,used as antispasmodic to lessen smooth muscle
spasm
•Increase heartrate by blocking Ach on the vagus therfore treating
arrhythmias
•Adjunt to anesthesia to protect against bradycardia, hypotension.
•Specific antidote to prevent muscarinic effect of Ach accumulation.

7. 3. Hyoscyamine, USP
•One of commercial sources is Egyptian henbane (Hyoscyamus muticus)
•Prepared from crude drug in manner similar to atropine and is purified
as the oxalate.
•Free base is obtained easily from this salt.
•Sparingly soluble in water, more soluble in ether or benzene, very
soluble in chloroform. Freely soluble in alcohol
•It is used as hydrobromide (popular because of its nondeliquescent
nature.)
•Tends to racemize to atropine sulphate rather easily in a solution,
atropine becomes more stable of the two.
•Treat disorders of the urinary tract than any other sntispasmodic.
•Used to treat spasm of the bladder
•Urinary stimulant
•Antispasmodic in therapy of peptic ulcer

8. 4. Hyosyamine sulfate, USP. ( Levsin sulphate)
•White, odorless, crystalline compound of a deliquescent nature
also affected by light.
•Soluble in water and alchohol, insoluble in ether.
•Solution is acidic to litmus
•Drug used as an anticholinergic in the same manner and for the
same indication as atropine and hyoscyamine.

9. 5. Scopolamine ( hyoscine)
•Isolated from the mother liquor remaining from the isolation of hyoscyamine.
•Hyoscine is the older name of this alkaloid.
•Levo component of racemic mixture known as atroscine.
•racemized readily in the presence of dilute alkali.
•Slightly soluble in water but very soluble in alcohol, chloroform or ether.
•Forms crystalline salts with most acids, with hydrobromide being most stable
and most accepted.
•Prevent motion sickness( transdermal form)
•Act as CNS depressant.

10. 6. Scopolamine Hyrdobromide, USP (hyoscine hydrobromide)
•Occur as white or colorles crystal, granular powder.
•Odourless and effloresce in dry air.
•Freely soluble in water, soluble in alcohol, slightly soluble in chloroform and
insoluble in ether.
•Action is on thehigher nerve centers.
•Readily cross blood-brain barrier
•Causes confusion in ederly.
•Cause to sink in restful dreamless sleep followed by period of approx. Same
length in which the patient is semiconscious state.
•Twilight sleep- term used for temporary amnesia with administration with
morphine.

11. 7. Hamotropine Hydrobromide, USP. (Homatrocel)
•Occur as white crystal or crystalline powder that is affected by light
•Soluble in water and alcohol, less soluble in chloroform an insoluble in
ether
•Solutions are incompatible with alkaline substances, which precipitate
free base
•Used topically to paralyze the ciliary structure of eye and to effect
mydriasis
•Behaves like atropine but weaker and less toxic
•Acts more rapidly but less persistent than atropine in the eye
•15-20 minutes to dilate the pupil and subsides in about 24 hours

12. 8. Hamatropine Methylbromide, USP.
• Bitter, white, odourless powder and affected by light
•Readily soluble in water and alcohol but insoluble in ether
•The ph of a 1% solution is 5.9 and a 10% solution is 4.5.
•Transported poorly across blood-brain barrier because of
quartenary ammonium group therefore has fewer stimulant
properties than atropine.
•It does have all characteristic peripheral parasymphatetic
depressant properties of atropine and is used to reduce
oversecreation and relieve GI spasm.

14. 9. Ipratropium Bromide (Atrovent)
•Quarternary ammonium derivative of atropine
•Freely soluble in water and ethanol but insoluble in chloroform and ether.
•Salt is stable in neutral and acidic solutions but rapidly hydrolyzed in alkaline
solutions.
•Used in inhalation teraphy producing dilation of bronchial smooth muscle for
acute sthma attacks.
•Bronchodilation by competitive inhibiton of cholinergic receptors bound to
smooth muscle of bronchioles.
•Slow onset of action within5-15 mins after being administered ( should not be
used for acute asthma attacks)
•1-2 hours the peak therapeutic dose
•6hours effect last
•Half life is 3.5 hours

15. 10. Tiotropium Bromide (Spiriva)
•Antimuscarinic used as inhalation device to deliver
the drug into lungs.
•For treatment of COPD. ,chronic bronchitis and
emphysema
•18mcg is the standard dose. Once daily.

17. Synthetic Cholinergic Blocking Agents
*Aminoalcohol Esters*
•Solanaceous alkaloids are agreed to be potent parasympatholytics , but
have undesirable property of producing wide range of effects through
their non specific blockade of autonomic function. Therefore, synthesis
of compounds possessing specific cholinolytic ly action has been very
desirable field of study.
•Early research was carried out in pre-and post world war 2 before
muscarinic subtypes were known.

18. Products
1. Clinidium Bromide, USP. (Quarzan)
•White,almost odorless crystalline powder that is optically inactive
•Soluble in water and alcohol and very slightly soluble in ether and benzene
•Librax- combination of minor tranquilizers chlordiazepoxide
•For treatment of GI complains
•Suggested for peptic ulcer, hyperchlorhydria, ulcerative or spastic colon,nervous
stomach and others.
•Contraindicated in glaucoma and other conditions that may be aggravated by
parasympatholytic action, such as prostatic hypertrophy in elderly men, which could
lead to urinary retention.

19. 2. Cyclopentolate Hydrochloride ,USP. (Cyclogyl)
•Crystalline ,white , odorless solid
•Very soluble in water, easily soluble in alcohol and slightly soluble in ether.
•1% solution has ph of 5.0 to 5.4
•Used only for its effect on the eye acting as parasympatholytic
•Mydriatic in the management of iritis, keratitis and choroiditis
•Has one half of antispasmodic effect of atropine and non irritating when
instilled repeatedly in the eye
•Neutralize with 1%-2% pilocarpine nitrate solution, recovery in 6 hours.
•Supplied in ready made ophthalmic solution in concentration of 0.5%-2%

20. 3. Dicyclomine Hydrochloride, USP.(Bentyl)
•Binds more firmly to M1 and M3 receptors
•1/8 of the neurotropic activity of atropine and twice the
musculotropic activity of papaverine.
•Used for various spasmolytic effect of various smooth muscle spasm,
particularly those associated with GI tract.
•Usefull in dysmenorrhea, pylorospasm and biliary dysfunction.

21. 4. Eucatropine Hydrochloride USP
•1,2,2,6-tetramethyl-4-piperidyl mandelate hydrochloride
•Odorless,white, granular powder
•Neutral solution to litmus
•Soluble in water, freely soluble in alcohol and chloroform, almost
insoluble in ether.
•Less potent than atropine,although action is almost parallel.
•Used topicallyin 0.1 ml dose of mydriatic in 2% solution or in a form
of small tablets
•Dilation takes place in about 30 mins and eye return to normal in 2-3
hours.

22. 5. Glycopyrrolate, USP.
•3-hydroxy-1,1dimethylpyrrolidinium bromide a-cyclopentylmandelate
(Robinul)
•White, crystalline powder
•Soluble in water and alcohol. Insoluble in ether and chloroform
•Posesses atropine-like effects at adequate dosage level
•Side effects also similar to atropine
•Potent antagonist of M1 receptor
•Low incidence of tachycardia
•Rarely causes CNS disturbance
•Adjunt in the management of peptic ulcer and GI ailments associated with
hyperacidity
•Hypermotility and spasm

23. 6. Mepenzolate Bromide
•3-hydroxy-1,1-dimethylpiperidinium bromide benzilate
(Cantil)
•Relieve pain,cramps and bloating and help curb diarrhea.

24. 7. Methanteline Bromide, USP.
•Diethyl(2-hydroxyethyl) methylammonium bromide xanthenes-9-carboxylate
(Banthine Bromide)
•White, slightly hygroscopic crystalline salt
•Soluble in water producing solution of ph 5
•Aqueous solution are not stable and hydrolyze in few days
•Bromide form is very hygroscopic chloride
•Introduced in 1950 is potent anticholinergic agent acting on nicotinic
cholinergic recptors of both sympathetic and parasympathetic system
•Indicated in gastritis, intestinal hyoermotility, bladder irritability, cholinergic
spasm,pancreatitis, hyperhidrosos and peptic ulcer
•Contraindicated in glaucoma

25. 8. Oxyphencyclimine HCL
•1,4,5,6-tetrahydro-1methy-2pyrimidinyl methy a-
phenylcyclohexaneglycolate monohydrochloride (Daricon, Vistrax)
•Introduce in 1958 promoted as pperipheral anticholinergic-
antisecratory agent
•Reduce both volume and acid content of gastric juices
•Low toxicity in comparison with many available anticholinergics
•Absorbed from GI tract and duration of action is up to 12 hours
•Suggested for use in peptic ulcer, pylospasm and functional bowel
syndrome.

26. 9. Oxybutynin
•4-diethylaminobut-2-ynly2-cyclohexy-2-hydroxy-2-phenyl-ethanoate (Oxytrol)
•One one the first agents developed to exploit the effects that cholinergic blocking
agents have on bladder.
•Result in less urinary incontinence, urgency and frequency.
•Competitive antagonism on M1 M2 M3 receptors

27. 10. Trospium Chloride
•3a-benziloy-loxynortropane-8-spiro-1-pyrrolidinium chloride ( Sanctura)
•Also a competitive antagonist of muscarinic receptors and is use to
manage over active bladder
•11. Solifenacin Succinate
•(Vesicare)
•Competitive antagonist of muscarinic subtypes
•Selectivity for bladder over other tissues such as salivary glands

28. Aminoalcohol Esthers
•Used as antiparkinsonian drugs rather than
conventional anticholinergics.

29. Products
1. Benztropine Mesylate, USP
•3a-(diphenymethoxy)- a H,5Ah-tropane methanesulfonate ( Cogentin)
•Anticholinergic, antihistaminic and local anesthetic properties .
•Antiparkinsonian agent
•About as potent agent as atropine and share some of its side effects
•Does not produce central stimulation instead exert sedative effect of
antihistamines
•Caution is exercised in patients with glaucoma

30. 2. Orphenadrine Citrate
•N,N-dimethyl-2-(o-methyl-a-phenylbenzyloxy)ethylamine citarate ( Norflex)
•Introduced in 1957 and closely resembles diphenhydramine structurally but
lower antihistaminic effect and higher anticholinergic action.
•Lacks sedative effect of diphenhydramine
•Best used as adjunct to other agents such as benztropine,procyclidine in the
treatment of paralysis agitans.
•Adjunct to other measures to relieve pain of local muscle spasm.

31. Aminoalcohols
•Development of aminoalcohol as
parasympatholytics took place in 1940s. It was soon
established that these antispasmodics were equally
efficacious in parkinsonism.
•Structural feature common on all aminoalcohol
anticholinergics is the y-aminopropanolol
arrangement.

32. Products
1.Biperiden USP
•a-5 norbornen-2-yl-a-phenyl-1-piperidinepropanol (Akineton)
•introduced in1959, has relatively week visceral anticholinergics but strong
nicotinolyic action in term of its ability to block nicotine-induced convulsion.
•Neurotropic action is low on intestinal musculature and blood vessel
•Strong musculatropic action about equal to papaverine.
•Mydriatic action in the eye but much lower than atropine.
•Mininimizing side effects of Parkinson syndrome.

33. 2. Procyclidine Hydrochloride, USP.
•a – cyclohexyl-a- phenyl-1-pyrrolidinepropanolol-hydrochloride (
Kemadrin)
•intoruced in 1956
•clinically useful for its ability to relieve voluntary muscle spasticity by its
central action therefore, has been used for its success in the treatment of
Parkinson’s.
•Toxicity is low, but when dosage is high side effects is noticeable.

34. 3. Tridihexethyl Chloride, USP.
•3-cyclohexyl-3-hydroxy-3-phenylpropyl)triethylammonium chloride ( Panthilon)
•White, bitter, crystalline powder.
•Freely soluble in water and alcohol, aqueous solution is neutral in reaction.
•Peripheral atropine-like activity dominates.
•Has antispasmodic and antisecretory activities
•Valueless in treating Parkinson’s.
•Useful for adjunctive therapy in wide variety of GI disease
•More effective in gastric hypersecretion than in hypermotility and spasm.
•Best administered IV

35. 4. Trihexyphenidyl HCL, USP.
•a – cyclohexyl-a-phenyl-1-piperidinepropanol hydrochloride (Artane, Tremin ,
Pipanol)
•introduced in 1949
•half as active as atropine as an antispasmodic but has milder side effects
•about as toxic as atropine
•treatment of Parkinsonism and relieves mental depression associated with the
condition.
5. Tolterodine
•2-[3-[bis(1-methyl-ethy)amino]-1-phenyl-propyl]-4-methyl-phenol
•Acts on M2 and M3 subtype receptors
•Reduction of smooth muscle tone allowing greater volume of urine to be stored
in the bladder

36. Aminoamides
•Same type of molecule as aminoalcohol group with
the important exception that the polar amide group
replaces the corresponding polar hydroxyl group.

37. 1. Isopropamide Iodide, USP.
•3-carbamoyl-3,3-diphenylpropyl)diisopropylmethylammoniumiodide
(Darbid)
•The only drug of this class that is used.
•Bitter,white to pale yellow crystalline powder
•Sparingly soluble in chloroform and alcohol.
•Introduced in 1959
•Producing atropine-like effects peripherally.
•Does not cause sympathetic blockade at the ganglionic level except
at high dosage.
•Has long duration of action as long as 12 hours.
•Used as adjunctive therapy in the treatment of peptic ulcer and
other GI conditions associated with hypermotility and hyperacidity.
•Contraindicated in glaucoma,prostatic hypertrophy..etc.

38. Miscellaneous
•Structural modification can be found in these
drugs. Each has a typical bulky group
characteristics of the usual anticholinergic
molecule.

39. 1. Diphemanil Methylsulfate USP.
•4-(diphenylmethylene)-1,1-dimethylpiperidiniummethylsulfate (Prantal)
•Acts as effective parasympatholytic by blocking the nerve impulses of
parasympathetic ganglia.
•Does not invoke sympathetic ganglionic blockade.
•Highly specific in activating gastric secreation and GI motility
•Useful in the treatment of peptic ulcer and hyperhydrosis in low doses(50
mh twice daily)
•Administered between meals.

40. 2. Ethopropazine HCL, USP.
•10-[2-(diethylamino0propyl]phenothiazinemonohydrochloride (Parsidol)
•Introduced in 1954
•Useful in the symptomatic treatment of parkinsonism
•Drowsiness and dizziness is the most common side effect
•Contraindicated to patients with glaucoma.

41. 3.Papaverine HCL,USP.
•6,7-dimethoxy-1-veratrylisoquinolone hydrochloride
•Isolated by Merck in 1848 from opium
•Main effect is spasmolytic of the smooth muscle,acting
as direct, nonspecific relaxant on vascular,cardiac and
other smooth muscle.
•Often called nonspecific antagonist.

42. Nondepolarizing Competitive
Ganglionic Blocking Agents
-these compounds posses the affinity to attach to a
nicotinic receptor sites specific for ACh but lack
intrinsic activity necessary for impulse
transmission.
-prolonged administration results in tolerance,
Drugs falling in this class :
•Tetraethylammonium salts
•Hexamethonium
•Trimethapahan

43. Neuromascular Blocking Agents
•These are agents that block the transmission of Acetylcholine at
the motor end plate
•Primary as adjuvants in surgical anesthesia to obtain relaxation
of skeletal muscle.
•Used in orthopaedic procedures such as alignment of fractures
and correlation of dislocation
•Curariform or having curarimimetic activity are the
therapeutically useful compounds of this group. Which were
obtained from curare.

44. Curare and Curare Alkaloids

45. •In 1935 a pure crystalline alkaloid ,d-
tubocurarine chloride was isolated from a
plant possessing paralyzing action of curare.
•Chondodendron tomentosum (
Menispermaceae ) was the known botanic
source of the drug isolated by Wintersteiner
and Dutcher in 1943.
•Intocostrin was a standardized and purified
curare tradename. The solid content which is
almost one half tubocurarine solids.

46. •1.Tubocurarine Chloride, USP
•Prepared from crude curare by purification and crystallization.
•Occurs as a white to grayish white ,odorless crystalline powder soluble in
water. Stable to heat sterilization on aqueous solution.
•A nondepolarizing blocking agent used for its paralyzing action on voluntary
muscles.
•Its action is inhibited by AChE inhibitors such as neostigmine . and then
necessitated in respiratory embarrassment caused by overdosage.
•Drug is inactive orally
•Paralysis last for 2 hours although binds only for 1ms.
•Half-life is 89 minutes.

47. Synthetic Compounds with
Curariform Activity
1.Atracurium Besylate
•(Tracrium)
•2.5 times more potent than d-tubocurarine. Duration of action is
much shorter.
•AChE inhibitors antagonize its paralyzing effect.
•2. Doxacurium Chloride
•(Nuromax)
•A long acting nondepolarizing blocking agent .
•Has no vagolytic activity.
•Used as skeletal muscle relaxant in surgical procedures that last
90minutes.

49. 3. Gallamine Triethiodide, USP (Mivacron)
•Has strong vagolytic effect and persistent decrease in neuromascular function
after successive doses that cannot be overcome by cholinesterase inhibitors.
•Contraindicated to patients with myasthenia gravis
•Action is cumulative
•Antidote is neostigmine.
•4.Mivacurium Chloride
•(Mivacron)
•Short acting nondepolarizing agent used as adjunct to anesthesia to elax
skeletal muscle.
•AChE can prolong rather than reverse the effects of the drugs.

50. 5.Pancuronium Bromide
•(Pavulon)
•Based on the alkaloid malouetine
•Acts on nicotinic receptor and ion channels inhibiting normal ion fluxes
•Marketed at concentrations 1 or 2 mg/ml IV
•5x more potent than tubocurarine chloride
•Action is increased by inhilations anesthetics such as ether and halothane.
•6. Pipercurium Bromide
•(Arduan)
•Action similar to the latter

51. 7. Succinylcholine Chloride,USP
•(Anectine, Sucostrin)
•White odorless,crystalline substance freely soluble in water to give solutions
with ph of about 4.
•Stable in acidic solutions and unstable in alkali
•Has very short duration of action and quick recovery
•Muscular paralysis
•Anticholinestresase does not antagonize the action of this drug instead prolongs
it.
•It is a a muscle relaxant
•May be used either for short or long periods of relaxation
•Suitable for continous IV drip administration
•Should not be used with thiopental