Thioxanthene neuroleptics

Conventional antipsychotic (neuroleptic, thioxanthene, dopamine 2 antagonist)... 

Reduction of the exocyclic double bond generally decreases neuroleptic activity in this series. Some of these compounds, however, show other activities. Methixene (44), for example, is used as an antispasmodic agent. It is prepared by alkylation of the sodium salt of thioxanthene (43) with w-methyl-3-chloromethyl-piperidine. ... 

But (i) Effect only antagonised by some neuroleptics, phenothiazines-YES thioxanthenes-YES butyrophenones-NO (metoclopromide inactive)... 

Chlorpromazine is technically described as a phenothiazine, as are thioridazine and fluphenazine. Together with their structural analogues the thioxanthenes (e.g., clopenthixol) and the butyrophenones (e.g., haloperidol), the phenothiazines comprise the three major families of typical neuroleptics. They were developed in the late 1950s and early 1960s (Table 11.3). All these drugs block dopamine receptors, principally the D2 subtypes, with an affinity that correlates highly (r = +0.90) with their clinical... 

Thioxanthenes A family of typical neuroleptics including clopenthixol. 

Whatever the underlying causes may be, neuroleptic medications are the most effective treatment for schizophrenia. All antipsychotic medications have some form of dopamine receptor antagonism and they are distinguished by their chemical class. The phenothiazines include chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), fluphenazine (Prolixin), and prochlorperazine (Compazine). The thioxanthenes include chlorprohixine (Taractan) and thiothixene (Navane). Butyrophenones are represented by haloperidol (Haldol). Loxapine (Loxitane) is a dibenzoxapine, and molindone (Moban) is a dihydroindolone. 

A number of different compounds of the piperidine and piperazine series with p-fluorobuty-rophenone group substitutions at the nitrogen atom display significant neuroleptic activity (haloperidol, trifluperidol, droperidol, methorin). There is a considerable interest in butyrophenone derivatives as antipsychotic agents as well as in anesthesiology. They exhibit pharmacological effects and a mechanism of action very similar to that of phenothiazines and thioxanthenes in that they block dopaminergic receptors. However, they are more selective with respect to D2 receptors. 

Neuroleptic structurally different from the phenothiazines, thioxanthenes, and bu-tyrophenones... 

In my opinion, one may assume a priori that these criteria will not be fulfilled first, if the dopamine-sensitive adenylate cyclase was really involved in the parathormone secretion, the patients treated with neuroleptics and especially with the most potent drugs on the sites (phenothiazine and thioxanthene derivatives) would have normally revealed marked changes in their parathormone secretion, just like as is the case for the prolactin secretion in fact such changes have never been observed secondly, a recent report clearly indicates that the injection of dopamine in man does not modify parathormone secretion although a marked decrease in prolactin was observed (21). There is no receptor without physiological response the study of receptor requires a multidisciplinary approach. 

A variety of drugs that block DA receptors are available for clinical use, and even more for experimental purposes. These drugs, also referred to as neuroleptics, include phenothiazines (e.g., chlorpromazine), thioxanthenes (e.g., chlorprothixene), butyrophenones (e.g., haloperidol), diphenylbutylpiperidines (e.g., pimozide), and dibenzodiazepines (e.g., clozapine). The major medical applications for these drugs are in the treatment of severe psychiatric illnesses, certain movement disorders, emesis and intractable hiccough. 

The differential clinical actions of DA blockers on the DA receptor subtypes have not been defined with precision. Most neuroleptics appear to act at both D-1 and D-2 receptors. Some differences exist, however. The thioxanthenes bind to sites related to both DA receptor subtypes, but the butyrophenones seem to prefer sites assocaited with D-2 receptors, binding only weakly to those identified with D-1 receptors. Sulpiride, molindone and metoclopramide are relatively selective D-2 antagonists. 

For the two antidepressants (imipramine and maprotiline), the bioisosterism is geometrical insofar that the dihedral angle a formed by the two benzo rings is comparable a = 65° for the dibenzazepine and a = 55° for the dibenzocyclohepta-diene [12]. This angle is only 25° for the neuroleptic phenothiazines and for the thioxanthenes. In these examples, the part of the molecule modified by isosterism is not involved in the interaction with the receptor. It serves only to position correctly the other elements of the molecule. 

Teflutixol, a poly substituted piperazine-thioxanthene structure, neuroleptic and antipsychotic [55837-23-5],1709... 

Thioxanthenes differ from the phenothiazines by having a carbon atom instead of a nitrogen atom in the central ring. The thioxanthenes can be represented as two geometric stereo-isomers Cis(Z)- and trans(E)- compounds. Only the cis Z)- compounds have been shown to be neuroleptically active [83]. 

Various neuroleptic drugs, particularly low-dose phe-nothiazines and thioxanthenes, commonly cause blurred vision secondary to their anticholinergic activity. This is primarily a nuisance, except in the rare patient with closed-angle glaucoma. 

Potentially serious skin reactions are best treated by withdrawing the offending agent and switching to a structurally unrelated neuroleptic drug. When the offending agent is a phenothiazine, non-phenothiazines such as haloperidol or molindone may be preferable to the more closely related thioxanthenes. 

The structure-activity relationships of the thioxanthenes mimic that of the phenothiazines. Aromatic substitution at the 2 position enhances neuroleptic potency (309). Replacement of the dimethyl amino function by selected piperazine derivatives as in clo-... 

Thioxanthenes and Thioxanthones. - Several possible metabolites of the neuroleptic chlorprothixene (241) have been synthesized for example, the geometric isomers of 3-, 4-, 6-, and 7-hydroxy- and -methoxy-derivatives. Lucanthrone (242 = H) is known to have anti-tumour properties,... 

Phenothiazine derivatives (e.g., chlorpromazine) Thioxanthene derivatives (e.g., thiothixene) Butyrophenone derivatives (e.g., haloperidol) Dihydroindolone derivatives (e.g., molindone) Dibenzoxazepine derivatives (e.g., loxapine) Atypical neuroleptics (e.g., sulpiride, pimozide, and clozapine)... 

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