Piperazine chlorpromazine

Incorporation of a second nitrogen atom in the side chain, particularly when that atom is part of a piperazine ring, was found to give a series of major tranquilizers similar in biologic activity to chlorpromazine, but of much increased potency. Alky-... 

Derivatives bearing a piperazine moiety (e.g., trifluperazine, fluphena-zine) have greater antipsychotic potency than do drugs containing an aliphatic side chain (e.g., chlorpromazine, triflu-promazine). However, their antipsychotic effects are qualitatively indistinguishable. 

This group of drugs is subdivided into three subgroups depending on the type of substitution on the nitrogen atom of the phenothiazine ring. The subgroups are phenothiazines with an aliphatic side chain (chlorpromazine, promazine, triflupromazine), piperazine derivatives (acetophenazine, fluphenazine, perphenazine, prochlorperazine, trifluoperazine), and piperidines (mesoridazine, thioridazine). 

Zuclopenthixol is a thioxanthene of high potency with general property similar to the chlorpromazine. It has a piperazine side-chain. 

Three subfamilies of phenothiazines, based primarily on the side chain of the molecule, were once the most widely used of the antipsychotic agents. Aliphatic derivatives (eg, chlorpromazine ) and piperidine derivatives (eg, thioridazine ) are the least potent. These drugs produce more sedation and weight gain. Piperazine derivatives are more potent (effective in lower doses) but not necessarily more efficacious. Perphenazine, a piperazine derivative, was the typical antipsychotic drug used in the CATIE study described in the following text. The piperazine derivatives are also more selective in their pharmacologic effects (Table 29-1). 

Many chromatographic separations of isotopologues of various amines that are biologically active or have drug properties have been achieved. Among these are perdeuteronucleosides 137 a tetracyclic 3,3,4,4-c/4-piperazine with antimigraine activity 138 the tetracyclic antidepressant mianserin with 2H or 3H in the A-methyl 139 A-CH3-tritiated chlorpromazine... 

The piperazine phenothiazines, as exemplified by fluphenazine, are the most potent members of the phenothiazine group, being at least 50 times more potent than chlorpromazine. Because of the structure of their side chain, members of this series lack anticholinergic, antihistaminic, adrenolytic and sedative effects. However, they are more likely to cause extrapyramidal side effects. 

Hepatotoxicity may be as frequent with piperidine and piperazine phenothiazines as with chlorpromazine, despite previous suggestions that the toxicity of these compounds is less. 

High doses of piperazine can enhance the adverse effects of chlorpromazine and other phenothiazines (667). 

Sturman G. Interaction between piperazine and chlorpromazine. Br J Pharmacol 1974 50(l) 153-5. 

Antipsychotics can be divided by chemical class phenothiazines, e.g. chlorpromazine. fluphazine and thioridazine butyrophenones, e.g. haioperidol thioxanthines, e.g. nupenthixol benzamides, e.g. sulpiride diphenylbutyl-piperazines, e.g. pimozide dibenzazepines, e.g. clozapine. None is entirely selective, but in schizophrenia they act mainly at dopamine D2 receptors, though clozapine has important actions at D4 receptors. Those antipsychotics with markedly depressant side-effects are also, somewhat misleadingly, known as major tranquillizers. 

Figure 12-20 schematically represents a putatively preferred conformation for the piperazine type of phenothiazine antipsychotic. As numerous analogs were tested, it became apparent that the B site of these molecules had the strictest specificity requirements for optimum activity. The activity screened to establish an index of comparison to CPZ (the chlorpromazine index, Cl) was the ability of a compound to block the conditioned escape response of rats. It is expressed as a decimal fraction or multiple of CPZ. The absolute... 

Phenothiazine derivatives cause postural or orthostatic hypotension. This may be more pronounced in patients with reduced vascular volume resulting from acute hemorrhage or dehydration, and when used with diuretic agents. Hypotension is more frequent with phenothiazine derivatives having either an aliphatic substitution on NIO (e.g., chlorpromazine) or a piperidine substitution on NIO (e.g., mesoridazine or thioridazine). It occurs less frequently with compounds containing a piperazine substitution (e.g., trifluoperazine). The hypotension is due to direct vasodilation and an alpha-adrenergic-receptor-blocking effect. The pressor effects of epinephrine can be reduced, blocked, or reversed by appropriate doses of chlorpromazine. 

NORTRIPTYLINE, see Tricyclic antidepressants OXAZEPAM, see Benzodiazepines PERPHENAZINE, see Phenothiazines, piperazine PHENELZINE, see MAO inhibitors PHENOTHIAZINES, ALIPHATIC (chlorpromazine, triflupromazine)... 

Simultaneous l-(2-pyrimidinyl)piperazine, metabolites, amitriptyline, chlorpromazine, clomipramine, duphenazine, imipreimine Noninterfering caffeine, diazepam, desipramine, mianserin, zimeldine Interfering haloperidol... 

Phenothiazines are divided into three groups. These are aliphatic, piperazine, and piperidine. Each category has different side effects (see Table 15-2). The aliphatic group produces a strong sedative effect, decreases blood pressure, and may moderate extrapyramidal symptoms (EPS). Chlorpromazine is a member of this group. 

An isolated case of convulsions in a child was attributed to the use of piperazine followed by chlorpromazine. 

Chapter 15. The molecule of chlorpromazine was subjected to many changes, one of which was to provide a long-acting form for discharged patients. Thus an injection of 25 mg of fluphenazine enanthate, dissolved in oil, provides maintenance therapy for 2 to 3 weeks. Fluphenazine is 10- 3-[4-(2-hydroxyethyl)-piperazin-l-yl]propyl -2-trifluoromethylphenothiazine, obviously derived from chlorpromazine which is 10-(3-dimethylaminopropyl)-2-chlorophenothiazine 12,110). 

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