Much like the other neuroleptics, thioxanthenes are prescribed for patients suffering from schizophrenia. In addition to this, some of the drugs in this group possess specific characteristics that justify their application in clinical medicine.

Table 2 includes a comparative summary of these three classes of neuroleptics, listing some of the common risks of antipsychotic medications [10,11,12,13,14,15,16,17,18,19].

The first thioxanthene, chlorprothixene, was found to have an excellent effect in schizophrenic patients [20]. Chlorprothixene had been used in the treatment of neuroses, not only due to its sedative and calming effects but also due to its low level of toxicity and side effects. Treatment with rather low doses results in favorable results in neuroses with anxiety, tension, insomnia, psychosomatic disorders, and depression. Chlorprothixene had also been found useful for treating alcoholics and alcohol psychoses [21].

Flupenthixol is the highly potent thioxanthene analogue of the phenothiazine fluphenazine [22]. Flupenthixol possesses a distinct anxiolytic property. At low and, sometimes, rather higher doses, this drug is effective against hallucinations and delusions. Flupenthixol manifests stimulating or activating properties in low doses; sometimes even apathetic patients show greater alertness. Schizophrenic patients treated with chlorpromazine, levomepromazine, or other thioxanthenes are sometimes given flupenthixol in low doses as aftercare. It can control psychotic symptoms without affecting the alertness or working ability of the patients [9,23]. The action of flupenthixol is much similar to that of trifluoperazine, but the former induces much less extra-pyramidal effects [24]. Flupenthixol is often prescribed for mood stabilization when psychiatric patients suffer from depressive neurosis. During the early 1970′s, intensive clinical studies repeatedly proved the excellent efficacy of flupenthixol over other neuroleptics in depressive patients [25,26]. Administration of this drug in low dosages does not usually produce side effects, however, sleep disturbances may occur in some patients who are treated after 5 pm [9].

Clopenthixol has a narrower field of application compared to chlorprothixene, although often it produces quick action on patients suffering from delusions, aggressiveness, destructiveness, impulsiveness, and even hallucination, and has also been proven to be definitely better than chlorpromazine for treating paranoid schizophrenics [27]. It produces highly satisfactory results in paranoids and catatonics [28]. Treatment with clopenthixol may start with a low dose followed by a gradual increase. However, therapy has to be continued on a regular basis with one tablet in the evening.

Much like the phenothiazines, thioxanthenes exhibit varied pharmacological actions, peripheral as well as central. However, therapeutic uses of these compounds depend on their psychopharmacological activity. The neuroleptic potency of a synthesized thioxanthene depends on the structure of the side chain in position 9. The compounds with β-hydroxyethylpiperazinopropyl or β-hydroxyethylpiperidinopropyl side chains are more potent neuroleptically than those with a dimethylaminopropyl side chain [29]. The antagonistic effect against methylphenidate-induced stereotypes in mice was employed to determine the exact duration of neuroleptic action of a compound. It was found that the peak effect was between 2 and 6 h, and by 24 h, effects of all the compounds were gone [9,30].

Neuroleptics are known to block the dopamine-induced formation of cyclic adenosine monophosphate (cAMP). In an elaborate study, Iversen et al. (1974) [31] observed that Z-flupenthixol was the most potent neuroleptic among all the test phenothiazines, thioxanthenes, and tyrophenones. Interestingly, they noted that E-flupenthixol was completely inactive.

It is known that neuroleptics have to be administered to psychiatric patients on a long term basis. In 1974, Moller et al. [32] observed that the antagonistic effect of neuroleptics undergoes tolerance development in animal models after prolonged therapy. They reported that when rats were pre-treated with flupenthixol for 12 days, followed by 3 days withdrawal, the antagonistic potency against apomorphine stereotypes was decreased. This reduction in potency subsequently gradually disappeared.

Neuroleptics are known for their α-adrenolytic function. Between phenothiazines and thioxanthenes, the adrenolytic activity was found to be more prominent in the Z-isomers of chlorprothixene, flupenthixol, and clopenthixol, while chlorpromazine and fluphenazine (which has no E/Z center) revealed much less activity [33].

Nasrallah & Tandon (2013) [9] observed that there was a moderate reduction in adrenaline pressor response after administration of either chlorprothixene or flupenthixol to anaesthetized cats. Furthermore, in vagotomized cats, the carotid occlusion reflex was reduced. After administration of chlorprothixene in these animals, respiration remained unaffected, although initially there was a transient rise in respiratory minute volume, due to increased tidal volume. Intravenous infusion of chlorprothixene or flupenthixol in conscious dogs resulted in the fall of blood pressure, without any change in pulse pressure. Treatment of dogs exhibiting tachycardia with flupenthixol resulted in a normalization of heart rate for 15 min [9,14].