-1-

hydroxyl group contributes to the strength of binding, probably by hydrogen bonding to an electron-rich portion of the receptor surface

-2-

-3-

The solanaceous alkaloids have been modified by substitution various acids for tropic acid portion or making a quaternary of the nitrogen in Troponal, or scopine with a methyl halide. -4-

Since quaternary compounds can be absorbed, other less efficient mechanisms for absorption probably prevail. Quaternary ammonium compounds combine reversibly with endogenous substances in the gut, such as mucin, to form neutral ionpair complexes. These complexes penetrate the lipid membrane by passive diffusion.

-5-

Atropine occurs in the form of optically inactive, white odorless crystals possessing a bitter taste. It is not very soluble in water (1:460, 1:90 at 80C) but is more soluble in alcohol. It is metabolized in the liver to several products, including tropic acid and tropine.

Atropine Sulfate, USP :

-6-

The action of atropine or its salts is the same. It produces a mydriatic effect by paralyzing the iris and the ciliary muscles and, for this reason, is used by the oculist in iritis and corneal inflammations and lesions. Atropine is administered in small doses before general anesthesia to lessen oral and air passage secretions and, when administered with morphine, to lessen the respiratory depression induced by morphine. Atropine causes restlessness, prolonged pupillary dilation, and loss of visual accommodation use it as an anesthetic premedicant to reduce excessive salivary and airway secretions and to prevent vagal reflexes atropine or belladonna has been used as an antispasmodic to lessen the smooth muscle spasm )griping) often associated with catharsis. Atropine is a specific antidote to prevent the muscarinic effects of ACh accumulation, such as vomiting, abdominal cramps, diarrhea, salivation, sweating, bronchoconstriction, and excessive bronchial secretions.which are symptoms of the poisoning by organophospher compounds.

-7-

Ipratropium Bromide :
is a quaternary ammonium derivative of atropine. Ipratropium bromide is used in inhalation therapy to produce dilation of bronchial smooth muscle for acute asthmatic attacks.

Scopolamine :
Scopolamine (hyoscine) is found in various members of the Solanaceae.

scopolamine is effective in preventing motion sickness. The action is believed to be on the cortex or the vestibular apparatus. Whereas atropine stimulates the CNS, causing restlessness and talkativeness, scopolamine usually acts as a CNS depressant.

-8-

One of the major developments in the field of aminoalcohol esters was the successful introduction of the quaternary ammonium derivatives as contrasted with the tertiary amine-type esters synthesized originally. The important feature in many of the synthetic anticholinergics used as antispasmodics is that they contain a Quaternary nitrogen, presumably to enhance activity. The initial synthetic quaternary compound methantheline bromide has served as a forerunner for many others. These compounds combine anticholinergic activity of the antimuscarinic type with some ganglionic blockade to reinforce the parasympathetic blockade. The accompanying formula shows the portion of the atropine molecule (enclosed in the curved dotted line) believed to be responsible for its major activity.

Products : Clidinium Bromide, USP :

Uses : -9-

Peptic ulcer, hyperchlorhydria, ulcerative or spastic colon Contraindicated in glaucoma.

Eucatropine Hydrochloride, USP:

possesses the aminoalcohol moiety characteristic of one of the early local anesthetics (e.g., the acidic portion of the ester by being a mandelate instead of a benzoate.

-eucaine) but differs in

The action of eucatropine hydrochloride closely parallels that of atropine, although it is much less potent than the latter It is used topically as a mydriatic.

Methantheline Bromide, USP :

- 10 -

Aminoalcohol Ethers:

- 11 -

The aminoalcohol ethers thus far introduced have been used as antiparkinsonian drugs rather than as conventional anticholinergics (i.e., as spasmolytics or mydriatics). In general, they may be considered closely related to the antihistaminics. Comparison of orphenadrine with the antihistaminic diphenhydramine illustrates the close similarity of structure.

Orphenadrine Citrate:

is closely related to diphenhydramine structurally but has much lower antihistaminic activity and much higher anticholinergic action. This drug is used for the symptomatic treatment of Parkinson disease. The drug combats mental sluggishness, akinesia, adynamia, and lack of mobility.

Aminoalcohols :
- 12 -

The structural feature for this class are :

Biperiden, USP:
It has a relatively weak visceral anticholinergic, but a strong nicotinolytic, action . Therefore, its neurotropic action is rather low on intestinal musculature and blood vessels . It has a relatively strong musculotropic action, which is about equal to that of papaverine, in comparison with most synthetic anticholinergic drugs. The drug is used in all types of Parkinson disease. It is contraindicated in all forms of epilepsy.

- 13 -

Trihexyphenidyl chloride, USP:

The side effects usually found with effective anticholinergic therapy occur with the use of this drug. These are dryness of mouth, mydriasis. It is contraindicated in patients with obstruction at the bladder neck, prostatic hypertrophy, stenosing gastric and duodenal ulcers.

- 14 -

Isopropamide Iodide, USP:

White crystalline powder that is only sparingly soluble in water but freely soluble in chloroform and alcohol.

It is used as adjunctive therapy in the treatment of peptic ulcer and other conditions of the GI tract associated with hypermotility and hyperacidity. It has the usual side effects of anticholinergics (dryness of mouth, mydriasis, difficult urination) and is contraindicated in glaucoma, prostatic hypertrophy.

Tropicamide, USP:
is an effective anticholinergic for ophthalmic use when mydriasis is produced by relaxation of the sphincter muscle of the iris, allowing adrenergic innervation of the radial muscle to dilate the pupil. tropicamide has modest selectivity for the

M4 receptor.

- 15 -

Diphemanil Methylsulfate, USP:

It isolated by Merck in 1848 from opium , in which it occurs to the extent of about 1%. Although its natural origin is closely related to morphine papaverine hydrochloride are unlike those of morphine. Its main effect is as a spasmolytic on smooth muscle. Because of its broad antispasmodic action on ACh muscarinic receptors, it is often called a nonspecific antagonist - 16 -

- 17 -

- 18 -

The principal therapeutic application has been in the treatment of hypertension through blockade of The sympathetic pathways.

- 19 -

Trimethaphan Camsylate, USP:

This ganglionic blocking agent is short acting and is used for certain neurosurgical procedures in which excessive bleeding obscures the operative field

- 20 -

- 21 -