Anticholinergic activity antipsychotic agents

Chlorpromazine is the best known representative of the aliphatic phenothiazines. Although it is considered to be a low potency agent it is still frequently used. It is one of the most sedative antipsychotic agents and is therefore very effective in the treatment of agitated and violent patients. Extrapyramidal effects are seen with a rather low incidence. However it displays marked anticholinergic activity. There have been reports of hepatotoxicity, also in patients with previously normal hepatic function, due to chlorpromazine. Alimemazine and triflupro-mazine are other representatives from this group. 

Of the systemic antihistamines, the ethanolamines, including diphenhydramine, have significant antimuscarinic activity. In addition, the antipsychotic agents, particularly the phenothiazines such as thioridazine (Mellaril), have well-dociunented anticholinergic properties. Therapeutic doses of tricyclic antidepressants, like amitriptyline hydrochloride (Elavil) and imipramine (Tofranil), produce significant anticholinergic actions and thus have the potential for ocular side effects. 

Some members of the class are extremely potent antipsychotic agents and Dn and D.i receptor antagonists. BP.S are extremely marked in some members of this class, which may. in pan. be due to a potent DA block in the striatum and almost no eompen.satory striatal anticholinergic block. Mott of the compounds do not have the structural features ixsociaied with effective anticholinergic activity. 

FIGURE 11 — 11. One compensation for the overactivity of acetylcholine that occurs when dopamine receptors are blocked is to block the acetylcholine receptors with an anticholinergic agent. Thus, anticholinergics overcome excess acetylcholine activity caused by removal of dopamine inhibition when dopamine receptors are blocked by conventional antipsychotics. This also means that extrapyramidal symptoms (EPS) are reduced. 

The side effects of these drugs are well known and have been summarized earlier (SED VIII, p. 313). Drugs with selective activity may be classified as antidepressants, antipsychotics, antihistamines, antispasmod-ics or antiparkinsonism agents and yet have anticholinergic actions as side effects. When two or more are given together the unwanted effects are more likely to arise. 

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