President Bashar al-Assad's regime appeared under severe pressure yesterday as fierce gun battles raged on the streets of the capital in what residents described as the worst fighting since the beginning of the 17-month-long uprising and a slew of senior defections continued.

The regime's tight control on Damascus appeared to be slipping as fighting broke out in several neighbourhoods close to the city centre and major transport arteries were blocked by protesters burning tyres. With his seat of power in turmoil, Mr Assad was dealt a further blow with reports of more senior regime figures defecting – this time the former head of Syria's weapons programme and another senior diplomat.

Free Syrian Army gunmen wielding automatic weapons crouched behind sandbags in an online video purporting to be filmed in the city's central Midan district as the sound of intense gunfire roared nearby. The men shouted "God is great" and flashed peace signs before the cameraman fled at the sound of a huge explosion.

In what activists said was the largest military deployment in the city so far, troops backed by armoured vehicles entered the neighbourhood yesterday morning and deployed along the major thoroughfares. Pro-rebel groups reported that the Free Syrian Army had destroyed an armoured vehicle and killed an unspecified number of security forces in the area, including several rooftop snipers. Though sporadic fighting is not uncommon in Damascus, the scale and intensity of the latest battles, which broke out on Sunday, is unprecedented.

"People are really scared," said a resident of the Old City. "The sound of the guns can be heard all the time. It's the worst fighting here since the uprising began and it's very close to the centre."

The violence has spiralled in the last few weeks, with the situation on the ground now generally considered a full-scale civil war.

The neighbourhoods of Kfar Sousa and Tadhamon and the Palestinian refugee camp of Yarmouk to the south were also the scene of clashes yesterday, as thick black smoke rose over the city skyline. "It seems there is a new strategy to bring the fighting into the centre of the capital," local activist Mustafa Osso told the Associated Press. "The capital used to be safe. This will trouble the regime."

Videos posted online showed protesters blocking the road out of the capital to Deraa in the south with burning tyres. The road to the airport was also reported to have been temporarily blocked as was Khalid Al Waleed Street in the heart of the city. With access for journalists severely restricted such reports are impossible to verify.

Recent defections have increased the isolation of the regime, although Assad's inner circle still remains largely unscathed. Maj Gen Adnan Sillu, the former head of Syria's chemical weapons programme, announced his defection in an online video he said he had taken up a post as the head of the joint military leadership of the FSA.

Farouk Taha, Syria's ambassador to Belarus until his mission ended six months ago, was summoned to return to the foreign ministry in Damascus but instead announced his defection, Syrian National Council sources told Asharq Al-Awsat newspaper.