In vivo Piroxicam Metabolites: Possible Source for Synthesis of Central Nervous System (CNS) Acting Depressants.
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.


CONCLUSIONS
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.
Department of Veterinary Physiology, Pharmacology and Biochemistry, College of Veterinary Medicine, University of Agriculture, P.M.B. 2373, Makurdi, Benue State. Nigeria.
Saganuwan A
SA
Saganuwan
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D002492:Central Nervous System Depressants / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D010894:Piroxicam / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002492:Central Nervous System Depressants; D010894:Piroxicam
Allosteric receptor; barbiturate; cytochrome P450 enzyme; depression; dopamine; piroxicam