Thiothixene actions

After dopamine was identified as a neurotransmitter in 1959, it was shown that its effects on electrical activity in central synapses and on production of the second messenger cAMP by adenylyl cyclase could be blocked by antipsychotic drugs such as chlorpromazine, haloperidol, and thiothixene. This evidence led to the conclusion in the early 1960s that these drugs should be considered dopamine-receptor antagonists and was responsible for the dopamine hypothesis of schizophrenia described earlier in this chapter. The antipsychotic action is now thought to be produced (at least in part) by their ability to block dopamine in the mesolimbic and mesocortical systems. 

May increase the effects of antihypertensive drugs except for guanethidine, whose antihypertensive actions thiothixene may antagonize... 

The neuroleptic (at first called tranquillizing ) action of these pheno-thiazines was later found in other chemical series, notably among the thioxan-thenes [e.g. chlorprothixene 12.111)]. and butyrophenones [e.g. haloperidol 12.112)]. At first, the dose of the butyrophenones was much lower than was needed for the other two categories, but now these too have low-dose examples such as perphenazine, trifluoperazine, fluphenazine, and thiothixene. ... 

A large number of papers appeared this year on some of the older phenothiazine type drugs (e.g. mesoridazine, flu-penthixol, chlorimpiphenin, clopenthixol, propericiazine, thiothixene). Few of these current reports add to our knowledge on the efficacy or mode of action of these drugs. 

An attempt to reduce the extrapyramidal side effects of the phenothiazines by the incorporation of anticholinergic properties into phenothiazines was reported. This was effected by the preparation of quaternary salts of chlorpro-mazine, trifluoperazine and perphenazine by the action of the oxime of phenacyl bromide on these compounds. Pharmacological results with these quaternary derivatives indicated a general loss of overall activity with a greater supression of extrag ra j-dal effects than loss of CNS depressant properties. The chemistry of thiothixene 16b and its related... 

The psycholeptic action, characteristic of these phenothiazines, was later found in other series, notably among the thioxanthenes [e.g. chlor-prothixine (75.74), Taractan ], and the phenylbutyrophenones introduced by Janssen in Belgium about 1958 [e.g. haloperidol (75.75)]. To-day a distinction is made between the high-dose psycholeptics, such as chloro-promazine and chlorprothixen, which have an additional sedative effect, and the low-dose psycholeptics, such as perphenazine, trifluoperazine, fluphenazine, haloperidol, and thiothixene, which have a strong, but purely psycholeptic, action. 

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