The Greatest Tox Scene in Opera

http://www.youtube.com/watch?v=dCWxbfFIflE

Mozart’s Cosi fan tutte has what is, beyond any argument, the greatest and funniest medical toxicology scene in all of opera. On this Saturday (April 26), the Metropolitan Opera Live in HD series will broadcast Cosi to theaters around the world,with James Levine conducting. As one who thinks that the 3 operas — The Marriage of Figaro, Don Giovanni, and Cosi fan tutte — written by Mozart and his librettist Lorenzo Da Ponte represent the greatest works of art in the history of the human race, I can’t wait. In anticipation, I am rerunning this post from several years ago:

There is an amazing toxicology-themed scene in the finale to Act I of Mozart’s Cosi Fan Tutte. In the opera, two young friends — Ferrando and Guglielmo — make a bet with an older cynic — Don Alfonso — that their fiances — Fiordiligi and Dorabella — will remain ever faithful. (If you’re having trouble sorting out these characters at home, you’re in good company.  Apparently, Mozart at times confused them in the manuscript to the opera.)  Keeping with the terms of the bet, the two friends disguise themselves as Albanian soldiers and pursue the other’s fiance. Initially unsuccessful, they pretend to swallow arsenic and collapse.  A doctor is summoned and appears, but it is actually Despina the maid in disguise.  The libretto continues:

DON ALFONSO:  . . . look at these poor fellows; they’ve taken poison; what can be done?

FIORDILIGI AND DORABELLA: Yes, doctor, what can be done?

DESPINA: First I must know the nature of this potion and reason it was taken; whether it was swallowed hot or cold, a little or much, in one draught or in several.

English Translation: Lionel Salter

After the doctor (Despina) determines the route and dose of the poison, and whether it was an acute or chronic ingestion, she pretends to cure the Albanians with a magnetic device discovered by Dr. Mesmer in Germany.

As often in Mozart, Cosi Fan Tutte intermingles the broadest farce with the most exquisite emotions.  Just like real life.

 

 

More about phenibut

phenibut_23.5 out of 5 stars

Phenibut (β-Phenyl-GABA): A Tranquilizer and Nootropic Drug. Lapin I. CNS Drug Rev 2001;7:471-481.

Abstract

Since posting about phenibut yesterday, I wondered how much medical literature existed describing its pharmacology and toxicology. This paper — not included in the  the initial accepted manuscript of O’Connell et al but referenced in the Wikipedia entry on phenibut — is the most complete discussion I found. However,  phenibut was first synthesized and used medically in the Soviet Union half a century ago and there undoubtedly is considerable literature published in Russian that I can’t access.

Here are some key points from this paper:

  • Phenibut (PB) is a GABA agonist, mostly at the GABAB receptor but to some extent also at GABAA receptors as well.
  • In addition, PB increases release of dopamine.
  • PB has no appreciable anticonvulsant effect.
  • Users quickly develop tolerance to the effects of PB.
  • In volunteers given a single oral dose, the plasma half-life of PB was 5.3 hours.
  • PB is excreted predominantly unchanged in the urine.

Wikipedia also referenced a 2008 abstract from the NYC Poison Control Center describing a case of PB withdrawal. a 40-year-old man presented to hospital with agitation, psychosis, hallucinations, and insomnia. He had stopped using PB 3 days previously. His vital signs were unremarkable except for a pulse rate of 110/min.

The patient required sedation with lorazepam βand intubation for chemical restraint. When he was extubated 4 days later his mental status had returned to baseline and there was no evidence of psychosis.
 

More about phenibut

phenibut_23.5 out of 5 stars

Phenibut (β-Phenyl-GABA): A Tranquilizer and Nootropic Drug. Lapin I. CNS Drug Rev 2001;7:471-481.

Abstract

Since posting about phenibut yesterday, I wondered how much medical literature existed describing its pharmacology and toxicology. This paper — not included in the  the initial accepted manuscript of O’Connell et al but referenced in the Wikipedia entry on phenibut — is the most complete discussion I found. However,  phenibut was first synthesized and used medically in the Soviet Union half a century ago and there undoubtedly is considerable literature published in Russian that I can’t access.

Here are some key points from this paper:

  • Phenibut (PB) is a GABA agonist, mostly at the GABAB receptor but to some extent also at GABAA receptors as well.
  • In addition, PB increases release of dopamine.
  • PB has no appreciable anticonvulsant effect.
  • Users quickly develop tolerance to the effects of PB.
  • In volunteers given a single oral dose, the plasma half-life of PB was 5.3 hours.
  • PB is excreted predominantly unchanged in the urine.

Wikipedia also referenced a 2008 abstract from the NYC Poison Control Center describing a case of PB withdrawal. a 40-year-old man presented to hospital with agitation, psychosis, hallucinations, and insomnia. He had stopped using PB 3 days previously. His vital signs were unremarkable except for a pulse rate of 110/min.

The patient required sedation with lorazepam βand intubation for chemical restraint. When he was extubated 4 days later his mental status had returned to baseline and there was no evidence of psychosis.
 

Toxicity from phenibut, a legal over-the-counter baclofen analogue

phenibut-300x3003 out of 5 stars

Phenibut, the appearance of another potentially dangerous product in the Univted States. O’Connell CW et al. Am J Med 2014 Apr 5 [Epub ahead of print]

Reference

This short case report describes a 25-year-old man who was brought to the emergency department after being found with decreased mental status and responsiveness.

On arrival at the hospital, his vital signs were stable and pulse oximetry 100% on room air. He was minimally responsive to painful stimuli. Neurological exam was non-focal and head CT unremarkable. A roommate reported that the patient had been taking 1.5 grams of “Phenibut” (purchased online) twice daily for the previous 4 days. The patient slowly improved and regained his normal level of consciousness over 7 hours.

Phenibut (also sold as “Noofen”) is β-phenyl-γ-aminobutyric acid. It has a structure similar to that of baclofen, differing only by the absence of the single chlorine on the aromatic ring:

Phenibut

Phenibut

 

Baclofen

Baclofen

Phenibut was discovered during the 1960s in Russia, where it is still used as a sedative. Like baclofen, it is a GABAB agonist. Central sedation from the direct action of phenibut was the likely cause of this patient’s clinical presentation, although the authors note that interaction with his prescribed medications (venlafaxine and mirtazapine) may have played a role.  No phenibut level was obtained.

Phenibut has not yet been restricted in the United States and seems to be readily available on the internet, sold for is purported use as an anxiolytic, sleep aid, or nootropic. There have been several descriptions of a phenibut withdrawal syndrome posted on internet discussion forums.

The authors report that they identified 3 addition cases of phenibut toxicity reported to poison control centers in California.

[Addendum 4/22/14]: For additional information about phenibut, click here.

 

 

Toxicity from phenibut, a legal over-the-counter baclofen analogue

phenibut-300x3003 out of 5 stars

Phenibut, the appearance of another potentially dangerous product in the Univted States. O’Connell CW et al. Am J Med 2014 Apr 5 [Epub ahead of print]

Reference

This short case report describes a 25-year-old man who was brought to the emergency department after being found with decreased mental status and responsiveness.

On arrival at the hospital, his vital signs were stable and pulse oximetry 100% on room air. He was minimally responsive to painful stimuli. Neurological exam was non-focal and head CT unremarkable. A roommate reported that the patient had been taking 1.5 grams of “Phenibut” (purchased online) twice daily for the previous 4 days. The patient slowly improved and regained his normal level of consciousness over 7 hours.

Phenibut (also sold as “Noofen”) is β-phenyl-γ-aminobutyric acid. It has a structure similar to that of baclofen, differing only by the absence of the single chlorine on the aromatic ring:

Phenibut

Phenibut

 

Baclofen

Baclofen

Phenibut was discovered during the 1960s in Russia, where it is still used as a sedative. Like baclofen, it is a GABAB agonist. Central sedation from the direct action of phenibut was the likely cause of this patient’s clinical presentation, although the authors note that interaction with his prescribed medications (venlafaxine and mirtazapine) may have played a role.  No phenibut level was obtained.

Phenibut has not yet been restricted in the United States and seems to be readily available on the internet, sold for is purported use as an anxiolytic, sleep aid, or nootropic. There have been several descriptions of a phenibut withdrawal syndrome posted on internet discussion forums.

The authors report that they identified 3 addition cases of phenibut toxicity reported to poison control centers in California.

[Addendum 4/22/14]: For additional information about phenibut, click here.

 

 

Tox Tunes #81: Junko Partner (Dr. John)

http://www.youtube.com/watch?v=BqfH_1xCSME

This is a great version of the blues standard from Dr. John‘s 1972 album Gumbo. The song has been covered by everyone from Professor Longhair to The Clash.

The liner notes call this song “the anthem of the dopers, the whores, the pimps, the cons”:

Lee Allenwails on this one, how many tenor choruses does he have, four? I love it! The song was first made popular by James Wayne’s hit on the “Sittin’ In” (Bob Shad’s) label. But it was a New Orleans classic; the anthem of the dopers, the whores, the pimps, the cons. It was a song they sang in Angola, the state prison farms and the rhythm was even known as the “jailbird beat”. Dudes used to come back with all different verses. The hard-core dopers couldn’t wait to hit the streets after their release so they could score again:

“Six months ain’t no sentence
One year ain’t no time
They got boys there in Angola
Doing nine to ninety-nine”

Meaning they had no intention of reforming even before beginning their sentence. It’a a song all New Orleans bands had to play; kind of a Calypso-oriented rhythm with a Cajun dialect. I heard it first on Poppa Stoppa’s radio show… Louis Jordan covered it later on, and he did an even heavier Calypso thing with it. The great thing on this record is our drummer Freddie Staehle’s laidback second-line drumming. This is classic New Orleans second line style where the drummer plays relaxed licks all around the beat, but with perfect time. You could call it “melody drums.”

[Liner notes from last.fm's barewires journal]