Scientists have created a compound that can reverse the effects of potentially lethal drugs

Drug overdoses in the United States have risen
dramatically over the past 20 years.
In 2020, nearly 92,000 people died from overdoses of illicit drugs and prescription opioids, more than five times the number of deaths in 2000, with synthetic opioids such as fentanyl being one
of the culprits.

Naloxone (an injectable drug, also known as nasal spray naloxone) has saved countless lives, but it is only effective for opioid overdoses, with other limitations
.
Now, to figure out a more general overdose treatment, a team of scientists at the University of Maryland has tested a compound — pillar [6]MaxQ (P6AS) — as an antidote
to methamphetamine and fentanyl.
Their findings, published today in the journal Chemistry, are very promising
.

Lead author Lyle Isaacs, a professor in the Department of Chemistry and Biochemistry at the University of Maryland, said, "Opioids already have a reversal agent in naloxone, but there are also various non-opioid abuses such as methamphetamine, PCP, methoxyephedrone, ecstasy (MDMA) and cocaine, which have no specific antidote
.
" "This is one of
the great opportunities for our company.
"

Laboratory tests in vitro but also in living organisms have shown that P6AS successfully isolates fentanyl and methamphetamine (a non-opioid stimulant) and mitigates their potentially lethal biological effects.
Additional in vitro tests have shown that P6AS also binds strongly to other drugs, including PCP, ecstasy and methoxyephedrine, suggesting that P6AS may one day be used against a wide variety of drugs
.

Although the synthesis and chemistry of P6AS was first documented in 2020 by Isaacs and Weijian Xue, a former postdoctoral fellow in the Department of Chemistry and Biochemistry, this study is the first to report the application
of P6AS in living organisms.

P6AS acts as a molecular container, meaning it binds to and isolates other compounds
in its central lumen.

Isaacs explains: "When we put molecules in containers, we can turn off their biological properties, thus reversing any effects
they may have.
" "We've measured interactions between our containers and various drugs of abuse, such as methamphetamine, fentanyl, ecstasy, PCP, etc.
, and we've found that this new container we've made can bind many of these drugs
very strongly.
"

Tests in living organisms showed that taking P6AS five minutes later could reverse the effects of methamphetamine, which is "still a bit short for reality," however, the effects of fentanyl can be reversed by giving P6AS after 15 minutes, which is closer to what federal drug reversal guidelines require
.

Unlike naloxone, which prevents drugs of abuse from binding to receptors in the brain, the UMD team's molecular vessels target the drug
directly in the blood.

"Our compounds absorb drugs from the blood, and we believe that this helps promote the excretion
of drugs in the urine," said Lyle Isaacs.
"This is called a pharmacokinetic process, and we try to minimize the concentration of free drugs in the body
.
"

Whether this compound helps promote the excretion of the drug from the body must be tested
experimentally.
If it works as the researchers imagined, it could be particularly useful for overdosing on fentanyl, which is 50 times more potent than heroin and 100 times
stronger than morphine.
Its potency and lingering effects in the body explain why some patients still overdose
after receiving naloxone treatment.
Isaacs believes that the excretion of fentanyl can help prevent this phenomenon, known as reanesthesia
.

Isaacs said it could be years before the new compound is approved for use in humans
.
However, he envisions that it could be delivered as an injection like naloxone, but could have wider applications
.
Isaacs believes it could even be used to treat overdoses of super-strong drugs like carfentanil, which has been linked
to a series of overdose deaths in recent years.

"There are other synthetic opioids that are much stronger than fentanyl, such as carfentanil, which is difficult to reverse
with naloxone.
" "Also, people get so much fentanyl that multiple doses of naloxone are needed, so there's room to develop a new improved drug that might help
in these cases.
" Vivian Sit and Lyle Isaacs are inventors
.