Popliteal lymph node enlargement and antibody production in the mouse induced by zimeldine and related compounds with varying side chains.
Structural requirements for induction of draining lymph node responses by the antidepressant drug zimeldine ((Z)-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridyl)allylamine) in mice were determined by comparison of its activity with that of metabolites and analogues having different side chains. Mice received 1.0 mg of the compounds into the hind footpad and the popliteal lymph nodes (PLN) were removed 7 days later to determine weight, cell number and antibody production. Compounds with a methylated (Z)-(homo)allylamine side chain induced a marked PLN weight gain in C57BL/6 mice and a significant increase of the PLN cell number and of the IgM and IgG production per 10(6) PLN cells in BALB/c mice. Moderate PLN weight increase, but no significant antibody formation was induced by the doubly demethylated zimeldine metabolite, while compounds without an aliphatic amine or having a saturated side chain lacked significant activity in all assays. The (E)-diastereomer of zimeldine induced significantly less PLN weight gain than zimeldine in C57BL/6 mice, but an equal increase of PLN cell number in BALB/c mice. IgM and IgG responses to the (E)-diastereomer were moderate and absent, respectively. The antihistaminic drug, brompheniramine, having a saturated side chain and a 2-pyridyl ring, induced less PLN weight and cell gain than zimeldine and failed to increase antibody formation. The capacity of the compounds to induce PLN responses appeared not related to their pharmacological potential to inhibit the reuptake of serotonin and noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
Thomas
C
C
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Punt
P
P
Warringa
R
R
Högberg
T
T
Seinen
W
W
Bloksma
N
N
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects*; D002452:Cell Count / Q000187:drug effects; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007717:Knee; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D015031:Zimeldine / Q000031:analogs & derivatives / Q000494:pharmacology*
D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015031:Zimeldine