Effects of disulfiram and coprine on rat brain tryptophan hydroxylation in vivo.
The effects of disulfiram and coprine on brain tryptophan hydroxylation, and on the brain-levels of serotonin and 5-hydroxyindole-3-acetic acid, were studied in 45 and 235 days old rats. Both drugs were found to affect the parameters measured. Disulfiram increased the rate of tryptophan hydroxylation and the serotonin level in young rats, while these parameters appeared to be unaffected in old disulfiram-treated rats. In contrast, coprine increased the rate of tryptophan hydroxylation and possibly also the serotonin level in old rats while no significant effects were seen in young coprine-treated rats. Regarding the 5-hydroxyindole-3-acetic acid concentration, this appeared to be increased by disulfiram in both age-groups, while no significant effects were found with coprine. The lack of similarity in the action of disulfiram and coprine, which are both potent aldehyde dehydrogenase inhibitors, suggests that the effects found were not caused by an impaired metabolism of monoamine-derived biogenic aldehydes.
Nilsson
G E
GE
Department of Zoophysiology, Uppsala University, Sweden.
Tottmar
O
O
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000367:Age Factors; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000447:Aldehydes / Q000502:physiology; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D004221:Disulfiram / Q000494:pharmacology*; D005973:Glutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D000447:Aldehydes; D005973:Glutamine; C014423:coprine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D014365:Tryptophan Hydroxylase; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram