Protection against burn, tourniquet and endotoxin shock by histamine, 5-hydroxytryptamine and 5-hydroxytryptamine derivatives.

ABSTRACT

1. 5-Hydroxytryptamine (5-HT), tryptamine, 5-methyltryptamine, 5-methoxytryptamine, N-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine, and histamine markedly protect mice subjected to burn, tourniquet and endotoxin shock. All of these compounds protect when given 30 min before the production of shock, but not when administered afterwards.2. The above compounds, as well as purines and purine derivatives have a similar chemical structure. Protection requires the compounds to contain a 5-membered ring with one unsubstituted N atom and a side chain with a basic N atom three atoms from the ring.3. All other biological amines tested without this chemical structure did not protect.4. Since the simplest compounds containing all the prerequisites for protection is histamine, this compound may play the key role in protection, for both 5-HT and purines release histamine from tissues.5. Protective doses of 5-HT and histamine prevent swelling of the injured area after tourniquet trauma and produce an increased bleeding volume and lower haematocrit value after burning. These actions of the drugs on the circulation may account for the increased survival after thermal trauma.