LOS ANGELES (AP) — Five people, including his personal assistant and two doctors, have been charged in connection with Matthew Perry's death in what prosecutors called a “broad underground criminal network” dedicated to getting the Friends star the powerful surgical anaesthetic that killed him.

The doctors preyed on Perry's history of addiction in the final months of his life last year to provide him with ketamine in amounts they knew were dangerous, US Attorney Martin Estrada said as he announced the charges on Thursday.

“They knew what they were doing was wrong,” Estrada said. "They knew what they were doing was risking great danger to Mr Perry. But they did it anyway.”

One doctor even wrote in a text message, “I wonder how much this moron will pay” and “Lets find out", according to an indictment unsealed on Thursday.

Perry died in October due to a ketamine overdose. Prosecutors said he had received several injections on the day he died from his live-in personal assistant, Kenneth Iwamasa, who found Perry dead later that day and was the first to talk to investigators.

Ketamine has seen a huge surge in use in recent years as a treatment for depression, anxiety and pain. While the drug is not approved for those conditions, doctors are free to prescribe drugs for so-called off-label uses.

Perry had been receiving regular ketamine infusion treatments for depression — in amounts not nearly enough to account for his death — from his regular doctors, who were not among those charged, authorities said.

When those doctors refused to give him more, he went in desperation to others.

“We are not talking about legitimate ketamine treatment," Estrada said. “We’re talking about two doctors who abused the trust they had, abused their licences to put another person’s life at risk.”

DEA Administrator Anne Milgram said in one instance that the actor paid $2,000 for a vial of ketamine that cost one of the physicians about $12. Perry paid the doctors about $55,000 in cash in the two months before his death, Estrada said.

Two of the people, including one of the doctors charged, were arrested on Thursday, Estrada said.

Two of the defendants, including Iwamasa, have pleaded guilty to charges already, and a third person has agreed to plead guilty.

Among those arrested were Salvador Plasencia, who is charged with seven counts of distribution of ketamine and also two charges related to allegations he falsified records after Perry's death.

Plasencia appeared in court briefly on Thursday afternoon and pleaded not guilty. He can be released after posting a $100,000 bond.

Plasencia’s attorney Stefan Sacks asked that his client be allowed to keep seeing patients at his practice when he was released.

He said he had already turned over his DEA licence to prescribe dangerous drugs and that the Perry case was “isolated”.

Assistant US Attorney Ian V. Yanniello objected, saying Plasencia had “essentially acted as a street-corner drug dealer”.

Magistrate Judge Alka Sagar ruled that Plasencia could treat patients only if they signed a document saying they had been informed of the charges against him.

“Ultimately, Dr Plasencia was operating with what he thought were the best of medical intentions,” and his actions “certainly didn’t rise to the level of criminal misconduct,” Sacks said outside the courthouse.

“His only concern was to give the best medical treatment and to do no harm,” Sacks said. “Unfortunately harm was done. But it was after his involvement.”

The other person arraigned in the case was Jasveen Sangha, who prosecutors described as a drug dealer known to customers as the “Ketamine Queen” — a moniker her lawyer derided as made-for-media consumption during her court hearing.

Ketamine supplied by Sangha caused Perry's death, authorities said.

Sangha pleaded not guilty and was denied bond. She had first been arrested in the case, charged with possession of ketamine with intent to distribute and released on bond in March, with authorities keeping Perry's involvement quiet.

A new indictment unsealed on Thursday alleges a direct connection to the actor's death. The judge ruled she should remain in custody, due to her concern over prosecutors’ contentions that she destroyed evidence and had used money from drug sales to fund a lavish lifestyle.

Plasencia could get up to 120 years in prison if convicted, prosecutors said. Sangha could get life in prison.

Records show Plasencia's medical licence has been in good standing with no records of complaints, although it is set to expire in October.

San Diego physician Mark Chavez has agreed to plead guilty to conspiracy to distribute ketamine.

Prosecutors allege Chavez funnelled ketamine to Plasencia, securing some of the drug from a wholesale distributor through a fraudulent prescription.

The prosecutor said the defendants exchanged messages soon after Perry's death referencing ketamine as the cause of death.

Estrada said they deleted messages and falsified medical records in an attempt to cover up their involvement.

Los Angeles police said in May that they were working with the US Drug Enforcement Administration and the US Postal Inspection Service with a probe into why the 54-year-old had so much of the surgical anaesthetic in his system.

Iwamasa found the actor face down in his hot tub on October 28 and paramedics who were called immediately declared him dead.

The assistant received the ketamine from Erik Fleming, who has pleaded guilty to obtaining the drug from Sangha and delivering them to Iwamasa. In all, he delivered 50 vials of ketamine for Perry's use, including 25 handed over four days before the actor's death.

Perry's autopsy, released in December, found that the amount of ketamine in his blood was in the range used for general anaesthesia during surgery.

But it had been ten days since his previous legitimate treatment, the medical examiner said, and the drug was typically metabolised in a matter of hours.

Estrada said that Plasencia had witnessed Perry freeze up and saw his blood pressure spike after injecting him with the drug but still left several vials with Iwamura for the actor to inject later.

Multiple requests for comment from lawyers for Chavez, Iwamasa and Fleming were not returned.

The medical examiner listed ketamine as the primary cause of death, which was ruled an accident with no foul play suspected, the report said. Drowning and other medical issues were contributing factors, the coroner said.

Perry had years of struggles with addiction dating back to his time on Friends, when he became one of the biggest television stars of his generation as Chandler Bing alongside Jennifer Aniston, Courteney Cox, Lisa Kudrow, Matt LeBlanc and David Schwimmer for ten seasons from 1994 to 2004 on NBC’s megahit sitcom.

Drug-related celebrity deaths have in other cases led authorities to prosecute the people who supplied them.

After rapper Mac Miller died from an overdose of cocaine, alcohol and counterfeit oxycodone that contained fentanyl, two of the men who provided him the fentanyl were convicted of distributing the drug. One was sentenced to more than 17 years in federal prison, the other to ten years.

Michael Jackson died in 2009 from a lethal dose of propofol, a drug intended for use only during surgery and other medical procedures, not for the insomnia the singer sought it for.

His doctor, Conrad Murray, was convicted of involuntary manslaughter in 2011. Murray has maintained his innocence.