INTRACELLULAR ACCUMULATION 



AND CRYSTALLISATION 



OF THE ANTITUBERCULOSIS RIMINO-COMPOUND, B.663 



M. L. CONALTY and R. D. JACKSON 



Laboratories, Médical Research Council of Ireland, 

 Trinity Collège, Dublin, Ireland 



The high antituberculosis activity of Rimino-compounds of the phenazine 

 séries has been demonstrated in thèse laboratories and confirmed in others. 

 It has provcd possible to demonstrate this activity even when treatment 

 has been completed one to four weeks before infection with tubercle 

 bacilli. It has been found that on administration of thèse compounds high 

 concentrations of the drugs are built up and are retained in the tissues. 

 The communication will deal specifically with one of thèse compounds, 

 B.663 (2-p-chloroanilino-5-p-chlorophenyl-3:5-dihydro-3-isopropyliminophe- 

 nazine). High tissue concentrations are due to the accumulation of drug 

 within macrophages, and continued treatment can resuit in intracellular 

 crystallisation. The séquence of events leading to this unique phenomenon 

 and the possible mechanisms involved, will be discussed. The effect of 

 thèse intracellular accumulations on cell activity, including phagocytosis, 

 will be described, together with détails of their influence on the histo- 

 logical pattem within varions tissues. 



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