A furious Daniil Medvedev suffered his fourth defeat in five matches as he crashed out of the St Petersburg Open to Reilly Opelka in his homeland on Thursday.

The top seed had ended a dismal losing streak with victory over Richard Gasquet in the first round and looked to be on course to advance again when he took the first set against Opelka.

But the 6ft 11in American responded to prevail 2-6 7-5 6-4 after successfully defending four Medvedev break points in the third set.

The world number six, who reached the US Open semi-finals before embarking on this desperate run, is the biggest scalp of Opelka's career.

"It is always a tough match, playing one of the best players in the world in general but especially at home," the victor said. "[It is] a great win for me.

"It was ugly for the first set and a half. I felt like I barely won any points on his serve, but part of that is just because of my opponent. Daniil is an absolute nightmare to play."

Medvedev smashed his racket into the court at the end of another frustrating contest.

Russia's other big names will at least fly the flag, as Andrey Rublev and Karen Khachanov progressed.

Rublev's comeback win over Ugo Humbert was a big one for the third seed, who is closing on a place in the ATP Finals. Canada's Denis Shapovalov is also in the running and remains in the hunt for the title this week.

Alexander Zverev eased through at the Cologne Indoors, beating Fernando Verdasco in straight sets, but Marin Cilic exited at the hands of Alejandro Davidovich Fokina.

Cilic led by a set and a break, then had two opportunities to break back in front at 5-5 in the second, before losing 3-6 7-6 (7-3) 6-2.

At the Sardegna Open, Casper Ruud was the victim of the day's biggest upset.

The third seed's prior five defeats since the ATP Tour returned in August had come against top-20 players, but he went down 6-2 6-1 to 101st-ranked Yannick Hanfmann.