Drug molecules, anticholinergics

The exact mode of action of oxamniquine is unknown [83]. The drug exhibits anticholinergic action its action on neuromuscular transmission has been demonstrated [119]. It has been suggested that oxamniquine (14) is converted enzymatically into a phosphate or sulphate ester (50), which then dissociates non-enzymatically to form the chemically reactive species 51. This intermediate then alkylates essential macromolecules of the schistosomes like DNA to give a Drug-DNA complex (52) (Scheme 5) [1,120,121]. The antischistosomal activity of oxamniquine is due to its ability to alkylate DNA. It does not intercalate with DNA, because the drug molecule is not planar, an essential structural requirement for intercalation. The lower mutagenic property of oxamniquine may, therefore, be due to the fact that it is not a DNA inter-calator [1],... 

With the possible exception of maprotiline, which is chemically a modified TCA with all the side effects attributable to such a molecule, all of the newer non-tricyclic drugs have fewer anticholinergic effects and are less cardiotoxic than the older tricyclics. Lofepramine is an example of a modified tricyclic that, due to the absence of a free NH2 group in the side chain, is relatively devoid of anticholinergic side effects. Thus by slightly modifying the structure of the side chain it is possible to retain the efficacy while reducing the cardiotoxicity. 

Thus, the anticholinergic activity of the alkaloid hyoscyamine is almost entirely confined to the (—)-isomer, and the (+)-isomer is almost devoid of activity. The racemic ( )-form, atropine, has approximately half the activity of the laevorotatory enantiomer. An anticholinergic drug blocks the action of the neurotransmitter acetylcholine, and thus occupies the same binding site as acetylcholine. The major interaction with the receptor involves that part of the molecule that mimics acetylcholine, namely the appropriately positioned ester and amine groups. The chiral centre is adjacent to the ester, and also influences binding to the receptor. 

Many drugs are racemates, including 13-blockers, nonsteroidal anti-inflammatory agents, and anticholinergics (e.g benzetimide A). A racemate consists of a molecule and its corresponding mirror image which, like the left and right hand, cannot be superimposed. Such chiral ( handed ) pairs of molecules are referred to as enantiomers. Usually, chirality is due to a carbon atom (C) linked to four different substituents ( asymmetric center ). Enantiomerism is a special case of stereoisomerism. Non-chiral stereoisomers are called diaster-eomers (e.g., quinidine/quinine). 

Benzatropine and etybenzatropine (ethylbenzatropine) are anticholinergic drugs. They represent attempts to combine atropine-like and antihistaminic effects in single molecules. The dose is determined individually and varies from 0.5 to 6 mg/day for benzatropine and 6 to 30 mg/day for etybenzatropine. Although the adverse reactions are essentially those of the anticholinergic drugs, sedation is very likely to occur and these drugs should not be used in patients who need to drive motor vehicles. Benzatropine has also been reported to cause rash, peripheral numbness, and muscular weakness. 

Funher. structural modification of cla.s.sic antimuscarinic agents can be found in the drugs described below. Each of them has the typical bulky group characteristic of the usual anticholinergic molecule. One modification is represented by ibe diphenylmethylene moiety (e.g.. diphcmanil) a sec-... 

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