Phenothiazines antipsychotic properties

Similar examples abound in most fields of therapeutics. For example, the major tranquilizer chlor-promazine—the first drug found to have true antipsychotic properties—is a trivial modification of phenothiazine, which was known for decades and used as a de-wormer for livestock. The parent phenothiazine, and many of its structural modifications, have no antipsychotic activity at all it is only certain minor structural modifications that have the essential pharmacologic and therapeutic properties. (Chlorpromazine also happens to be a classic example of the serendipitous empirical-clinical method of discovery of a drug s unique therapeutic value, a method described below.)... 

The first report of the distinct antimicrobial potentiality was made by Prof. Joseph Molnar and his associates in 1975 [71]. The drug was chlorpromazine, a phenothiazine discovered in 1950 for its antipsychotic property [ 14]. 

Antipsychotic medications have truly revolutionized the treatment of psychotic disorders. Their effectiveness is so vastly superior to previous treatments that they have ushered in a new era in the treatment of severe mental illnesses. Chlorpromazine (Thorazine) was first used in 1952 as a postoperative sedative. It was subsequently used as a sedative for psychiatric patients, and it was soon discovered that it had antipsychotic properties. Soon other "phenothiazines" were developed. 

The dihydroindolone molindone, though structurally different from the phenothiazine and butyrophenones, shares most of their antipsychotic properties and side effects. Its clinical effects resemble those of the piperazine phenothiazines. The drug s specific advantages, if any, are not readily apparent. 

Promethazine (Phenergan), a phenothiazine derivative that has no antipsychotic properties and has predominantly antihistaminic properties... 

Dopamine-receptor antagonists having antipsychotic properties, such as phenothiazine, butyrophenone, and thioxanthene derivatives, and Gl-stimulant drugs, such as metoclopramide, are contraindicated with pergolide. The... 

Phenothiazines are antipsychotic agents that can be used for their potent antiemetic and sedative properties (see Chapter 29). The antiemetic properties of phenothiazines are mediated through inhibition of dopamine and muscarinic receptors. Sedative properties are due to their antihistamine activity. The agents most commonly used as antiemetics are prochlorperazine, promethazine, and thiethylperazine. 

Tricyclic antidepressants—so called because of the characteristic three-ring nucleus—have been used clinically for four decades (Figure 30-1). They closely resemble the phenothiazines chemically and, to a lesser extent, pharmacologically. Like the latter drugs, they were first thought to be useful as antihistamines with sedative properties and later as antipsychotics. The discovery of their antidepressant properties was a fortuitous clinical observation. Imipramine and amitriptyline are the prototypical drugs of the class as mixed norepinephrine and serotonin uptake inhibitors though they also have several other properties. 

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. 

At about the same time, the drug imipramine was first produced. It was originally developed as a phenothiazine (antipsychotic), but was found to have antidepressant properties. Soon came amitriptyline, followed later by other "tricyclic" and "heterocyclic" antidepressants. 

Zovirax aciclovir. zucapsaicin capsaicin, zuclomifene clomiphene. zuclomiphene clomiphene. zuclopenthixol [ban, inn] (clopenthixol [ban, inn, usan] zuclopenthixol decanoate zuclopenthixol dihydrochloride Z-clopenthixol Clopixol ) is a thioxanthene with a piperizine side-chain, and has general properties similar to the phenothiazines, such as chlorpromazine. It is used as an oral ANTIPSYCHOTIC for the short-term management of acute psychotic and mania disorders, or the exacerbation of chronic psychotic disorders. The decanoate and hydrochloride forms can be given by deep intramuscular injection particularly for maintainance of patients with agitated and aggressive behaviour, zuclopenthixol decanoate zuclopenthixol. zuclopenthixol dihydrochloride zuclopenthixol. Zumenon oestradiol. 

These effects are more likely with antipsychotics, which have no intrinsic antichohneigic action (e.g. butyrophenones), and are less likely with antipsychotics with intrinsic anticholinergic properties (e g. phenothiazines). This is because of the reciprocal actions of DA and cholinergic systems in the basal ganglia. These side-effects, by definition, are also less likely with atypical antipsychotics. 

Procyclidine may reduce the antipsychotic effectiveness of haloperidol and phenothiazines, possibly by direct CNS antagonism related to its anticholinergic properties. Haloperidol and phenothiazine exert their effects in part by blocking the hyperactivity of dopaminergic transmission in the mesocortical and mesolimbic systems. Concomitant use with phenothiazine derivatives, especially thioridazine having pronounced anticholinergic effects, also increases the risk of anticholinergic adverse effects. Paralytic ileus may result from concomitant use with phenothiazines or tricyclic antidepressants. Concomitant use with alcohol and other CNS depressants increases procyclidine s sedative effects. 

Trifluoperazine, a phenothiazine antipsychotic with antiemetic properties (2 to 5 mg p.o. t.i.d.), is indicated in the management of manifestations of psychotic disorders (see Table 2). 

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