PMID- 9515226
OWN - NLM
STAT- MEDLINE
DCOM- 19980416
LR  - 20061115
IS  - 0378-6501 (Print)
IS  - 0378-6501 (Linking)
VI  - 23
IP  - 5-6
DP  - 1997
TI  - The new immunosuppressants, the malononitrilamides MNA 279 and MNA 715, inhibit 
      various graft-vs.-host diseases (GvHD) in rodents.
PG  - 167-73
AB  - The use of inbred mouse strains of defined genetic background has allowed for the 
      development of systems capable of reproducibly generating either an acute or 
      chronic graft-versus-host disease (GvHD). The malononitrilamides MNA 279 and MNA 
      715, analogues of the main metabolite of leflunomide, have been shown to directly 
      inhibit T-cell proliferation and B-cell functions. Therefore, they have been 
      studied in a local GvH reaction in the popliteal lymph node (PLN) assay in LBN 
      rats, on the development of an acute and lethal GvHD in B6C3F1 mice and on a 
      chronic autoimmune GvHD in BDF1 hybrid mice. In the PLN assay an oral 
      administration of various concentrations (7.5 to 50 mg/kg) of both MNAs inhibited 
      the localized GvH reaction dose-dependently and suppressed the lymph node 
      hyperplasia. Both MNAs also acted therapeutically in this assay when they were 
      given as late as day 4 or 5 after challenge. In the model of an acute lethal GvHD 
      the treatment of the GvH-B6C3F1 hybrid mice with the MNAs (2.5 to 20 mg/kg/day) 
      shortly after disease induction on days 3 to 12 resulted in a dose-dependently 
      improved survival rate. With 20 mg/kg of drugs, mortality of this 
      life-threatening GvHD was completely prevented and also other parameters like 
      splenomegaly, erythrocyte counts and hematocrit values were strongly suppressed. 
      Treatment of sensitized GvH-BDF1 hybrid mice in the chronic autoimmune-like model 
      with the MNAs (30 mg/kg/day), given on days 3 to 36 by oral gavage, resulted in 
      an improved survival rate, inhibited lymphadenopathy and splenomegaly, reduced 
      the levels of autoantibodies and other immunoglobulins like IgE and IgG1, 
      prevented proteinuria and the development of glomerulonephritis. Both MNA 279 and 
      MNA 715 can inhibit ongoing aberrant immune responses in animals suffering from 
      GvHD.
FAU - Schorlemmer, H U
AU  - Schorlemmer HU
AD  - Research Laboratories Hoechst-Marion-Roussel (HMR), DG-Rheumatology/Immunology, 
      Behringwerke AG, Marburg, Germany.
FAU - Kurrle, R
AU  - Kurrle R
FAU - Bartlett, R R
AU  - Bartlett RR
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Drugs Exp Clin Res
JT  - Drugs under experimental and clinical research
JID - 7802135
RN  - 0 (Alkynes)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Isoxazoles)
RN  - 0 (Nitriles)
RN  - 0 (X 910279)
RN  - 185915-33-7 (2-cyano-3-hydroxy-N-(4-(trifluoromethyl)phenyl)-2-hepten-6-ynamide)
SB  - IM
MH  - Alkynes
MH  - Animals
MH  - Disease Models, Animal
MH  - Graft vs Host Disease/drug therapy/prevention & control/*therapy
MH  - Graft vs Host Reaction/drug effects
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Isoxazoles
MH  - Lupus Erythematosus, Systemic/immunology/prevention & control
MH  - Lymph Nodes/drug effects/immunology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Nitriles/*therapeutic use
MH  - Rats
MH  - Rats, Inbred BN
MH  - Rats, Inbred Lew
EDAT- 1997/01/01 00:00
MHDA- 1998/03/27 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1998/03/27 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
PST - ppublish
SO  - Drugs Exp Clin Res. 1997;23(5-6):167-73.