Dissociation of immunosuppression by chlorpromazine and trifluoperazine from pharmacologic activities as dopamine antagonists.
Neuroleptic compounds may affect the immune system through a variety of mechanisms. Most possess a complex pharmacology, which makes specific, causal relationships difficult to discern. In this study, a series of experiments was performed to examine the effects of dopamine antagonists on a battery of immunologic parameters. Mitogen-induced lymphocyte proliferation in vitro was inhibited by haloperidol, chlorpromazine, and trifluoperazine at 10, 1 and 1 microM concentrations, respectively. Sulpiride and metoclopramide had no direct effect in vitro. In vivo lymphocyte proliferation was significantly reduced by chlorpromazine at the highest tested doses (12.5 and 15 mg/kg) and by trifluoperazine at the highest tested dose (30 mg/kg). All other dopamine antagonists had no significant effect on in vivo lymphocyte proliferation. A murine graft vs host (GVH) response was unaffected by haloperidol, sulpiride, and metoclopramide. Chlorpromazine and trifluoperazine exhibited significant inhibition of the GVH response at the highest doses only (15 and 30 mg/kg, respectively). In a picryl chloride induced delayed type hypersensitivity (DTH) assay, haloperidol, metoclopramide, and sulpiride had no effect. However, both chlorpromazine and trifluoperazine significantly reduced DTH-induced paw swelling at the higher doses (7.5 mg/kg, and 10 and 30 micrograms/kg, respectively). These studies indicate that the more specific dopamine antagonists (e.g. sulpiride, metoclopramide, and haloperidol) do not share the immunologic profiles of chlorpromazine and trifluoperazine, suggesting that these effects of chlorpromazine and trifluoperazine are not related to their dopamine antagonist properties.
Department of Immunology, Pulmonary, and Leukotriene Research, Eli Lilly and Co., Indianapolis, IN 46285.
R E
RE
Roudebush
P L
PL
Berry
N K
NK
Layman
L D
LD
Butler
H U
HU
Bryant
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D006087:Graft vs Host Reaction / Q000187:drug effects; D006968:Hypersensitivity, Delayed; D007107:Immune System / Q000187:drug effects*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology*
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D014268:Trifluoperazine; D002746:Chlorpromazine