[Synthesis and pharmacological study of orciprenaline and salbutamol derivatives]

The effect of replacing the basic aliphatic residue of orciprenaline [(A); R = isopropylamino] and salbutamol [(B); R = tert.butylamino] with: a) a heterocyclic amine; b) a basic residue containing a phenylcyclohexane radical had been studied. The synthesis of the compounds is outlined. They were tested in vitro for relaxation of histamine-induced spasm of tracheal chains and on the isolated Langendorff heart, and in vivo according to the Konzett and Rössler technique and for their action on the cardiovascular system. In all tests the new derivataives were less active than the reference substances; the only exception was (A) where R = 4-phenylpiperidine (M.G. 6604), which was almost as active as orciprenaline in the Konzett and Rössler test, had one third of its activity on isolated trachea and showed absolutely no influence on heart rate in vitro or in vivo. Its effect was not inhibited by beta-blocking agents; it therefore showed an antihistaminic profile.