A COMPREHENSIVE REVIEW OF XANTHENE AND THIOXANTHENE

A COMPREHENSIVE REVIEW OF XANTHENE AND THIOXANTHENE

Darakhshan Parveen * and Amrita Parle

Department of Pharmaceutical Chemistry, Delhi Pharmaceutical Sciences and Research University, Mehrauli - Badarpur Rd, Sector 3, Pushp Vihar, New Delhi, New Delhi, India.

ABSTRACT: Xanthene (or 9H-xanthene) is a parent active compound in which a pyran ring is combined with a benzene ring on both sides, whereas in thioxanthene, the oxygen of xanthene is replaced by a sulphur atom. Xanthene and thioxanthene are important classes of organic compounds which exhibit diverse pharmacological activities such as anti-spasmodic, anti-parkinsonian, anti-psychotic, anti-rhinitic, anti-inflammatory, anti-asthmatic, anti-ulcer, etc. This review covers various methods of synthesis of Xanthene and Thioxanthene. The pharmacoeconomic consideration of various marketed products of Xanthene and Thioxanthene are also discussed. It also covers the ongoing clinical trials of the upcoming Xanthene and Thioxanthene-based products and the newer indication of existing drugs. This review would be of immense use to researchers interested in Xanthene and Thioxanthene-based drugs. This review also helps the physician to preferably prescribe the cheaper brand for the patient's benefit with the help of pharmacoeconomic analysis discussed in the review.

Keywords: Xanthene, Thioxanthene, Marketed Products, Synthesis, Clinical Trial, Pharmacoeconomics

INTRODUCTION: Xanthene (or 9H-xanthene) is a parent active compound in which a pyran ring is combined with a benzene ring on both sides. Substitution at position 9 strongly influences their physical, chemical, and biological properties ¹. Xanthene has a wide range of pharmacological activities such as Antispasmodic ², Anti-Parkinsonian ³ and Anti-Psychotic ³. They are also used in the treatment of ulcers ⁴, rhinitis ⁵, urinary incontinence ⁶ and bronchitis ⁷. Thioxanthene is a compound in which a thiazine ring is combined with two benzene rings.

Thioxanthene is a chemical compound in which the oxygen atom in xanthene is replaced with a sulphur atom. Thioxanthene-based derivatives are used as typical antipsychotics ^{8, 9} in treating schizophrenia and other psychoses ³. It is also used as an antiparkinsonian, antispasmodic and antiemetic drug. They are used to treat bronchitis as well.

Marketed Drugs of Xanthene and Thioxanthene: The xanthene based marketed drugs along with their category, uses, brand names, a manufacturing company, pack size and price are covered in Table 1, while the thioxanthene based marketed drugs along with their categories, uses, brand names, a manufacturing company, pack size, and price are covered in Table 2.

TABLE 1: USES, BRAND NAME, MANUFACTURING COMPANY, PACK SIZE AND PRICE OF MARKETED DRUGS OF XANTHENE

Price of Propantheline: Available from: http://www.medlineindia.com. Price of Phloxine B: Available from: Scottsdental.com. Price of Oftasceine/ Fluorexon: Available from: https://worldsportsvision.com/product/higlo-strips/. Price of Methantheline: Available from: https://www.docmorris.de/vagantin-riemser-50-mgueberzogenetablet /10985801?sc= GKV# warenkorb. Price of Rose Bengal: Available from: www.amconlabs.com/product/1257/101/Rose-Bengal-Glostrips-by-Amcon/. Price of Fluorescein: Available from: https://www.medicineindia.org/brands-forgeneric/1822/fluorescein-sodium; https://www.1mg.com/drugs/floure-stain-strip-269741.

TABLE 2: USES, BRAND NAME, MANUFACTURING COMPANY, PACK SIZE AND PRICE OF MARKETED DRUGS OF THIOXANTHENE

Price of Pimethixene: Available from: https://consultaremedios.com.br/muricalm/1mg-ml-caixa-com-1-frasco-gotejador-com-10ml-de-solucao-de-uso-oral/p. Price of Metixene: Available from: https://en.adlershop.ch/p/6739/spasmo-canulase-100-tabletten; https://www.meduweb.com/spasmo-canulase-tablets/. Price of Thiothixene Manufactured by Mylan Inc.: Available from: https://www.empr.com/drug/thiothixene/. Price of Thiothixene manufactured by CVS Pharmacy, Kroger, Harris Teeter, Costco Pharmacy: Available from: https://www.singlecare.com/prescription/thiothixene. Price of Zuclopenthixol: Available from: https://www.medindia.net/drug-price/zuclopenthixol.htm. Price of Flupentixol: Available from: https://www.medindia.net/drug-price/flupentixol.htm. Price of Chlorprothixene Manufactured by Roche: Available from: https://www.ebay.com/itm/124784662630. Price of Chlorprothixene Manufactured by Zentiva KS and Lundbeck AS: Available from: https://pillbuys.com/shop/truxal-chlorprothixen-#/6051-brandmanufacturer-truxal_lundbeck_ as_denmark/2-dosage_form-pills/1604-package_size-50_mg_50_pcs

Pharmacoeconomic Analysis: Pharmacoeconomic considerations of different marketed preparations are described in Table 1 and Table 2.

Our observations indicated that some marketed drugs are manufactured by only one pharmaceutical company while many pharmaceutical companies manufacture some other drugs. We infer that:

1. Propantheline is marketed in India. It is manufactured by Sun Pharma and RPG Life Sciences Ltd.. The marketed preparation of Propantheline, which comes under the brand name of Spastheline Tablet 15mg manufactured by Sun Pharma, is cheaper compared to that of other Pro-Banthine Tablet 15mg manufactured by RPG Life Sciences Ltd.
2. Thiothixene is marketed in the US and not in India.
3. Generic marketed preparations of Thiothixene are manufactured by CVS Pharmacy, Kroger, Harris Teeter, Mylan Inc., and Costco Pharmacy, respectively. Thiothixene 2mg manufactured by CVS Pharmacy is cheaper among all, while the one manufactured by Costco Pharmacy is the costliest.
4. Flupentixol is marketed in India. It is manufactured by East West Pharma, Obsurge Biotech Ltd., Vidakem Life Sciences Ltd. and Jaiwik Biotech respectively. Flupen 0.5mg manufactured by East West Pharma is cheaper than Anxiset 0.5mg and Xolybex 0.5mg manufactured by Obsurge Biotech Ltd. and Vidakem Life Sciences Ltd.. Similarly, Flupen 1mg manufactured by East West Pharma is cheaper than Anxiset 1mg and Xolybex 1mg manufactured by Obsurge Biotech Ltd. and Vidakem Life Sciences Ltd., respectively.
5. Chlorprothixeneis marketed in the US and not in India. Roche manufactures it, Zentiva KS and Lundbeck AS. Chlorprothixen 50mg manufactured by Zentiva KS is cheaper than Truxal 50mg manufactured by Lundbeck AS. The physician should preferably prescribe the cheaper brand for the patient's benefit.

Synthetic Pathways: Several marketed preparations of xanthene and thioxanthene derivatives are available. The synthesis of various marketed xanthene-based drugs is elaborated in Table 3, while Table 4 elaborates on the synthesis of various marketed thioxanthene-based drugs.

TABLE 3: SYNTHESIS OF MARKETED DRUGS OF XANTHENE

Marketed Drug	Synthesis
Propantheline47
Phloxine B48
Methantheline47
Rose Bengal49
Fluorescein50

TABLE 4: SYNTHESIS OF MARKETED DRUGS OF THIOXANTHENE

Marketed Drug	Synthesis
Pimethixene7
Metixene51
Thiothixene47
1.       Zuclopenthixol/ Clopenthixol52
Flupentixol53
Chlorprothixene47

Ongoing Clinical Trials: Xanthene and thioxanthene derivatives are still being explored for various new indications. Propantheline, Methantheline, Rose Bengal, and Fluorescein are the existing marketed drugs, but they are explored for newer indications, whereas newer drugs such as Fluorescein lisicol and EC-17 are explored for various diseases. Xanthene-based drugs and their ongoing clinical trials are mentioned in Table 5, while thioxanthene-based drugs and their ongoing clinical trials are mentioned in Table 6. Zuclopenthixol and Flupentixol are the existing thioxanthene-based marketed drugs, but they are explored for newer indications.

TABLE 5: XANTHENE IN CLINICAL TRIALS

TABLE 6: THIOXANTHENE IN CLINICAL TRIALS

CONCLUSION: Xanthene and Thioxanthene are versatile but complicated structural moieties from which many drugs are synthesized. These drugs treat spasms, Parkinson's disease, psychosis, rhinitis, urinary incontinence, emesis, ulcer, and bronchitis. Even today, the interest in the xanthene and thioxanthene-based drugs is alive, which can be understood from the ongoing clinical trial for newer indications of existing drugs and newer drugs. This review would be of immense use to the researchers interested in xanthene and thioxanthene-based drugs as it covers not only marketed preparations of xanthene and thioxanthene but also the Pharmacoeconomic analysis synthesis as well as ongoing clinical trials.

ACKNOWLEDGEMENT: The authors are thankful to the Vice-Chancellor of Delhi Pharmaceutical Sciences and Research University (DPSRU) and the Director of Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR) for their motivational support and guidance.

CONFLICT OF INTEREST: Declared none

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    How to cite this article:

    Parveen D and Parle A: A comprehensive review on xanthene and thioxanthene. Int J Pharm Sci & Res 2022; 13(7): 2550-61. doi: 10.13040/IJPSR.0975-8232.13(7).2550-61.

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