Abstract |
SK&F 105685 (N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5] decane-2-propanamine+ ++ dihydrochloride), administered orally to adjuvant arthritic (AA) rats inhibited immune-mediated hindpaw inflammation with an ED50 of 20 mg/kg/day. Both prophylactic and therapeutic administration were effective in this model. In addition, SK&F 105685 inhibited skin wheal responses to purified protein derivative ( PPD) of tuberculin in AA rats and the development of hindleg paralysis associated with experimental allergic encephalomyelitis (EAE). Spleens of normal rats treated with SK&F 105685 were found to contain a population(s) of suppressor cells (SC) which inhibited the response of normal cells to Concanavalin A (Con A) in co-culture assays. The association between SC induction and anti-arthritic activity was determined by evaluating a series of chemically related azaspiranes in the AA rat model and for SC induction in normal rats. A statistically significant correlation was demonstrated (r = 0.79, P less than 0.001), indicating that SC induction may be responsible for the therapeutic activity of these compounds.
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Authors | A M Badger, M J Dimartino, J E Talmadge, D H Picker, D A Schwartz, J W Dorman, C K Mirabelli, N Hanna |
Journal | International journal of immunopharmacology
(Int J Immunopharmacol)
Vol. 11
Issue 7
Pg. 839-46
( 1989)
ISSN: 0192-0561 [Print] England |
PMID | 2532178
(Publication Type: Journal Article)
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Chemical References |
- Adjuvants, Immunologic
- Spiro Compounds
- SK&F 105685
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Topics |
- Adjuvants, Immunologic
(pharmacology, therapeutic use)
- Animals
- Arthritis, Experimental
(immunology)
- Autoimmune Diseases
(etiology, prevention & control)
- Disease Models, Animal
- Encephalomyelitis, Autoimmune, Experimental
(immunology)
- Female
- Lymphoid Tissue
(radiation effects)
- Male
- Rats
- Rats, Inbred Lew
- Spiro Compounds
(pharmacology)
- T-Lymphocytes, Regulatory
(drug effects)
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