Title:In vivo Piroxicam Metabolites: Possible Source for Synthesis of Central Nervous System (CNS) Acting Depressants
Volume: 17
Issue: 3
Author(s): Saganuwan A. Saganuwan*
Affiliation:
- Department of Veterinary Physiology, Pharmacology and Biochemistry, College of Veterinary Medicine, University of Agriculture, P.M.B. 2373, Makurdi, Benue State,Nigeria
Keywords:
Allosteric receptor, barbiturate, cytochrome P450 enzyme, depression, dopamine, piroxicam.
Abstract: Background: Piroxicam has been reported to be convertible to Central Nervous System
(CNS) acting agents. It has serious depressant effects at high doses.
Objective: In view of this, structures of piroxicam metabolites were assessed for possible conversion to
CNS depressants.
Methods: Literature search was carried out with intent to identifying piroxicam metabolites and the
possibility of converting them to CNS acting depressants.
Results: Piroxicam is convertible to hydroxymethylated metabolite which may be converted to barbiturates
such as thiopentone and thiamylal. Whereas cyclodehydrated metabolite may be converted to acetylcyclodehydrated
compound that may be in turn converted to acetylacetone and cyclohexamide.
However, carboxybenzothiazine metabolite may be converted to carboxamide compound, benzolactone
which is convertible to phenazone. Carboxybenzothiazine is also convertible to 2-aminopyridine
mepyramine and triplenamine. Conversion of carboxybenzothiazine to gamma aminobutyric acid and
phenothiazines such as chlorpromazine, thioridazine, fluphenazine and perphenazine is highly possible.
Conclusion: Structurally, barbituric compounds, carboxamide, cyclodehydrated, benzothiazine and
carboxybenzothiazine metabolites may act via dopamine and adrenergic receptors causing depression
of CNS activities. Piroxicam metabolites may also act via histamine, melatonin and potassium channel
receptors causing CNS depression.
