Immunological studies on paroxetine, a novel anti-depressant drug.
Paroxetine is a novel and selective neuronal 5-hydroxy-tryptamine uptake inhibitor with anti-depressant activity. Paroxetine was examined for its ability to induce adverse immunological reactions, either as a consequence of a specific immune response or by a direct or indirect effect on the immune system. Paroxetine did not react in vitro with protein amino or thiol groups, suggesting that it lacks the capacity to form potentially immunogenic hapten protein conjugates. No anti-paroxetine antibody was detected in plasma or serum samples from patients and rats following oral administration over prolonged periods, or from epicutaneously exposed guinea pigs, or from rabbits given paroxetine in Freund's adjuvant, suggesting that paroxetine does not have the capacity to elicit humoral immune responses. Guinea pigs epicutaneously exposed to paroxetine did not develop contact sensitivity, suggesting that it does not have the capacity to elicit cell-mediated immune responses. These results suggest that paroxetine lacks intrinsic immunogenicity. Anti-SRBC antibody plaque-forming cell responses in mice were unaffected by oral administration of paroxetine, and paroxetine had no significant effect on ex vivo and in vitro murine macrophage phagocytosis of opsonized SRBC or on ex vivo murine splenocyte mitogen responses, suggesting that paroxetine does not exert modulatory effects on the immune system or on macrophage function. These findings, together with the results of pre-clinical safety evaluation studies, suggest that paroxetine is unlikely to have immunotoxic effects.
Henderson
D C
DC
Beecham Pharmaceuticals Research Division, Biosciences Research Centre, Epsom, Surrey, England.
Edwards
R G
RG
Weston
B J
BJ
Dewdney
J M
JM
D000328:Adult; D000368:Aged; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000928:Antidepressive Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008875:Middle Aged; D017374:Paroxetine; D010880:Piperidines / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D000928:Antidepressive Agents; D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D017374:Paroxetine