Aliphatic phenothiazines

Phenothiazines, aliphatic chlorpromazine hydrochloride methotrimeprazine maleate promazine hydrochloride... 

Promazine HCl (6) Sparine Wyeth-Ayerst Phenothiazine (aliphatic amine) 200 40-1200 PO... 

Chlorpromazine HCl (1) Thorazine SmithKline Beecham Phenothiazine (aliphatic amine) 100 30-800 PO, IM, IV, rectal... 

Phenothiazines Aliphatic side-chains Piperidine Piperazine... 

Occasional Confusion amnesia disinhibition paradoxical excitement depression dizziness witiidrawal symptoms, including convulsions, on abrupt discontinuance (witiidrawal may be especially difficult with alprazolam) rebound insomnia or excitement Rare Hypotension blood dyscrasias jaundice allergic reactions paradoxical rage reactions stuttering with alprazolam BUPROPION, Anxiety agitation insomnia tremor anorexia BUSPIRONE, Dizziness headache nausea paresthesias diarrhea CHLORDIAZEPOXIDE, see Benzodiazepines CHLORPROMAZINE, see Phenothiazines, aliphatic CHLORPROTHIXENE, similar to Phenothiazines CLOMIPRAMINE, see Tricyclic antidepressants CLORAZEPATE, see Benzodiazepines CLOZAPINE... 

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

TRIFLUOPERAZINE, see Phenothiazines, piperazine TRIFLUPROMAZINE, see Phenothiazines, aliphatic TRIMIPRAMINE, see Tricyclic antidepressants... 

Fluorescein paraffin derivatives, waxes, hydrocarbons [140,141] aliphatic acids [142] hydroquinone and chlorinated derivatives [143] isoprenoids, quinones [111,144] oxathizine fungicides [145] barbiturates, phenothiazines [146]... 

For alkaloids, phenothiazines, penicillins, diuretics, tert, aliphatic amines and steroids Dissolve 200 mg to 1 g p-chlor in 100 ml dioxan, acetonitrile or toluene [2-11]. 

Derivatives of Methylene Violet 6 possessing long aliphatic chains are obtained by oxidative coupling of 3-acetoxyphenothiazine with a secondary amine in the presence of an oxidant such as iodine. The oxidative coupling of phenothiazine with amine is well known but in this case the reaction does not stop there but proceeds further at reflux temperatures to the phenothiazinone 74.9 Reduction of the latter dye and treatment with acetic anhydride yields the ballasted phenothiazine 6. Reaction of 75 with the dye chloroformate 70 yields the ballasted leuco dye developer 76. 

The answer is a. (Katzung, p 482.) Phenothiazines as a class and, in particular, the aliphatic phenothiazines are most likely to produce marked sedation. The mechanism of action for this effect is associated with its ability to block histamine and acetylcholine receptors. 

Chlorpromazine is an aliphatic phenothiazine antipsychotic used in schizophrenia and which may exacerbate parkinsonism. Co-careldopa is a combination of levodopa and the peripheral dopa-decarboxylase inhibitor, carbidopa. Co-careldopa, amantadine, entacapone and bromocriptine are all indicated in the management of parkinsonism. 

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). 

Piperazine derivatives inherent presence of stimulatory components.Phenothiazines with an aliphatic side chain and piperidine substituents have more of a sedative effect than piperazine derivatives. 

Phenothiazine antipsychotics can be divided in the aliphatic phenothiazines with a dimethylamino-propyl group, those with a piperazine structure and agents with a piperidine structure. 

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. 

Phenothiazines are classified on fhe basis of fheir chem-isfry, pharmacological acfions, and pofency. Chemical classifications include the aliphatic (e.g., chlorproma-ztne T/iorazme), piperidine (e.g., thioridazine Me//an7), and piperazine subfamilies. The piperazine derivatives are generally more potent and pharmacologically selective than the others. The thioxanthenes (e.g., thiothixene Navane) are chemically related to the phenothiazines and have nearly equivalent potency. The... 

Aliphatic amines act as reducing agents for the photoreduction of phenazine or phenothiazine dyes. It was found that polyamine induces a much higher photopotential than monoamine 91). The value of the photopotential was strongly dependent upon the number of amino or imino groups in one molecule when an oligoamine was used (Fig. 25). The electron transfer from the amine to the excited dye was proposed to be facile due to a bifunctional interaction between the dye and the adjacent free and protonated N-groups of the polyamine (24). 

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). 

The piperidine phenothiazines, as exemplified by the most widely used member of this series thioridazine, are approximately equivalent to the aliphatic phenothiazines but tend to be more sedative. Members of this series are therefore widely used for the more agitated, anxious psychotic patient. As their ability to cause parkinsonism appears to be less than with the other phenothiazines, possibly because of their potent central anticholinergic effects and slightly greater selectivity for mesocortical dopamine receptors, they are widely used to treat elderly psychotic patients. 

It has been suggested that the less potent sedative neuroleptic drugs (aliphatic or piperidine phenothiazines) lower the convulsive threshold more than the potent neuroleptic drugs (piperazine phenothiazines) (170). Variable and unpredictable effects on seizure activity related to butyrophenones have been reported (171). 

L1A1H4 reduction of amides to the aminomethylphenothiazines has been reported. - ° A procedure for obtaining long-chain aliphatic aldehydes has been developed using the action of LiAlH4 upon the amides obtained from carboxylic chlorides and phenothiazine (in position 10). Very good yields were thus obtained. ... 

Aliphatic and aromatic amines, alkaloids, amino adds, amino sugars, carboxylic and sul-fanfiic adds, drugs, indole derivatives, nucleobases, nucleosides, nucleotides, peptides, dipeptides, polypeptides, phenols, phenothiazine bases, steroids, sulfonamides, water-soluble food dyes... 

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. 

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