Eighth seed Stefanos Tsitsipas said after his shock first-round defeat at the US Open that he sometimes does not "feel inspired" on court.

The Greek 21-year-old, tipped as a future Grand Slam champion, lost 6-4 6-7 (5-7) 7-6 (9-7) 7-5 to Andrey Rublev.

"I feel like I'm doing the same thing over and over again, and my brain can't really take it any more," he said.

His surprise defeat came on a day where fourth seed Dominic Thiem and ninth seed Karen Khachanov also lost.

Austrian 25-year-old Thiem, twice a French Open runner-up, lost 6-4 3-6 6-3 6-2 to unseeded Italian Thomas Fabbiano, with 48 unforced errors his undoing.

Russian Khachanov, a quarter-finalist at Roland Garros in June, failed to convert nine break points and was beaten 4-6 7-5 7-5 4-6 6-3 by Canadian Vasek Pospisil.

'My brain can't really take it any more' - Tsitsipas

Tsitsipas, who could barely move between some points in the fourth set because of cramping, also became increasingly irritated with umpire Damian Dumusois, who docked the Greek a point for a time violation before the player was heard saying "you're all weirdos".

The Greek reached a career-high world number five last month, but may drop further down the rankings after his fourth straight defeat.

He said: "I feel like I'm doing the same routines on the court, the same execution, the same strategies."

On his argument with Dumusois, who also ruled he had been getting coaching from his father Apostolos, Tsitsipas added: "The umpire was very incorrect in what he was telling me during the match. He has something against me. I don't know why."

Russian Rublev, who stunned Roger Federer in Cincinnati in 62 minutes this month, said: "We played an amazing match. It was tough conditions for both of us. He started to cramp. I know what it's like; I was cramping too and tried not to show it. But this is amazing, winning matches like this gives you confidence."

The 21-year-old Russian, who sealed victory in three hours and 56 minutes, will face Gilles Simon in the second round.

Zverev comes through five-setter

Alexander Zverev, another of the younger generation hoping to challenge the dominance of the 'big three' of Roger Federer, Rafael Nadal and Novak Djokovic, made it into the second round but not without difficulty.

The 22-year-old German had seemed in control against Moldova's Radu Albot, taking the first two sets, before finding himself taken to a fifth. The world number six took charge in the decider, winning 6-1 6-3 3-6 4-6 6-2.

Meanwhile, Wimbledon semi-finalist and 10th seed Roberto Bautista Agut was knocked out with a 3-6 6-1 6-4 3-6 6-3 defeat by Mikhail Kukushkin.

Elsewhere, Croatian 2014 champion Marin Cilic, seeded 23rd, beat Slovak Martin Klizan 6-3 6-2 7-6 (8-6) and Italian 24th seed Matteo Berrettini defeated Frenchman Richard Gasquet 6-4 6-3 2-6 6-2.