The major event of Manuel's reign was the arrival of the Central Asian conqueror Tamerlane to Anatolia.

This led to the virtual destruction of the Ottoman Empire, which had threatened the existence of Manuel's domain, in the Battle of Ankara.

Although the Ottomans reconstituted their state after 10 years of civil war, this defeat extended the life and security of the Empire of Trebizond for several more decades.

[citation needed] When Tamerlane left Asia Minor in 1403, part of his army detached from the whole to visit the city of Kerasous and it was presumably by their ravages that the rule of Melissenos at Oinaion was destroyed.

The favor shown to him, however, aroused the anger of the native aristocracy because of his humble birth so they poisoned the minds of the people against the page.

At the same time, Alexios, covetous of the throne, raised the flag of revolt and demanded that the favorite be banished.

The nobles joined him and besieged Manuel in the upper citadel, finally forcing him to concede and banish the favorite from the palace.

This Komnenos had been the previous owner of the stallion Sphrantzes rode while campaigning in the Morea in 1429, and who married Eudokia the daughter of Manuel Palaiologos Kantakouzenos, but died before the couple could have children.