Barbiturates: Old Workhorse Dragged Out For a Stupid Netflix Series

Spoiler alert (or savior alert, depending on how you look at it):

In case the Netflix series The Perfect Couple is on your list of things to stream you might want to skip this article. But IMO you're better off skipping the series. It's SO trite. Tell me you haven't seen this plot before:

1. Meet a thoroughly repulsive stinking rich family (and a few equally repulsive friends)
2. They and a magnificently dumb poor family are brought together on Nantucket for the wedding of the rich guy to the poor girl.
3. Someone dies. Who could it be?
4. Each episode drops non-subtle hints, manipulating us into guessing who the killer is – it's someone different in every episode. (It is not Colonel Mustard in the library.)
5. The police, who may have written two tickets for parking meter violations in the last decade (Nantucket is very posh), go Sherlock Holmes on us and somehow figure out that it wasn't an accident; it was murder.
6. It goes without saying that none of these idiots who were suspects earlier in the series is the killer.
7. Of course, in an appalling display of banality, in the end, the only person who was not featured as a suspect – another idiot – is, of course, the killer.

Gee, how original.

Aside from venting a little, why should I bring this up? It's not like I'm some renowned movie critic. No, it's because as dumb as the series is, the pharmacology (there's a drug involved in the murder) is dumber. This I can criticize with some confidence. 

Hello writers! Welcome to the 21st century. They chose phenobarbital (Nembutal) as the putative murder weapon. Phenobarbital? Seriously? There were approximately zero prescriptions written for the stuff in the last decade (1). Let's leave the rousing climax for later and take a look at barbiturates, formerly enormously popular sleeping pills and sedatives, that were used well before the time of the Salk polio vaccine.

Barbiturates - relics of the pharmaceutical past

Barbiturates are derivatives of barbituric acid. (I hope no one died of shock from that revelation.) A look at the chemical structures makes this obvious.

(Formerly) common barbituates. From left to right: barbituric acid, phenobarbital (Nembutal), Seconal, sodium thiopental (aka "truth serum"). They are easily made from barbituric acid. 

Some history and pharmacology

Barbituric acid, which is not pharmacologically active, was first synthesized in 1864 by German chemist Adolf von Baeyer (not of aspirin fame). It was not until 1903 that chemists modified the molecule and discovered Veronal (barbital), the first active barbiturate. It became a very popular sleep aid and sedative and was followed by phenobarbital in 1912 and a few more in the ensuing 30 years.

However, although effective, the entire class suffered from safety issues, especially a narrow therapeutic index (2) and the potential for overdose (3) and addiction. When the first benzodiazepines, Librium and Valium, became available in the 1960s, barbiturates began to fall out of favor because benzodiazepines are much safer, so much so that it is virtually impossible to kill yourself with Valium.

Both barbiturates and benzodiazepines are central nervous system depressants that act upon GABA receptors in the brain, albeit in slightly different ways. Benzodiazepines do so more "gently," which accounts for their improved safety profile. 

Barbiturates for lethal injection

Barbiturates, especially sodium thiopental (4), were commonly used in the three-drug lethal injection protocol. First, sodium thiopental is used to induce unconsciousness. Then pancuronium bromide, which causes paralysis, is given followed by potassium chloride, which stops the heart.

While sodium thiopental may have been popular in prisons that carry out capital punishment, this did not sit well in Europe, where capital punishment is frowned upon. Hospira, the last company to make the drug, closed its plant in Italy partly due to pressure from the Italian government and the EU. This made it virtually impossible to procure the drug. For a while, prisons switched to pentobarbital, aka Nembutal, but this, too, became unavailable for the same reasons. The lack of availability of these drugs led states to try experimental combinations with ghoulish results, something I last wrote about in 2022. 

Back to Netflix

Part of the plot is that the poor girl's mother has some serious kind of cancer. She carries three phenobarbitol tablets in a little pouch (5) In case "things go downhill." (Mom said that she bought the pills from a street dealer. I don't think so. You'd have a better chance of finding someone selling a submarine on a street corner.)

But one of the repulsive characters finds Mom's stash, immediately recognizes the drug, and decides to steal one of them, which later gets used in the murder. When Mom sees she's missing one pill, she does a major freakout because now she doesn't have enough phenobarbitol to kill herself.

As a chemist, this got my attention right away. Is it even possible that there's a drug in which three pills will be fatal while two will not? Unlikely, because it would be a pharmaceutical hand grenade with the pin pulled. We never learn the dose of the phenobarbital pills, which aren't even made in the US. When they were made, the doses ranged from 15 to 100 mg. Let's pick the highest – 100 mg – just to be fair. 

A lethal dose of pentobarbital ranges from 2-10 grams (and can be higher) so Mom would have needed between 20 and 100 pills, each 100 mg, to do the job. This is one of the issues confronting people who seek physician-assisted suicide. It requires the person to swallow the contents of 100 pills, each 100 mg, of Seconal or Nembutal. To get around this, the pills are opened and dissolved in water or juice, making a solution that is difficult to drink and keep down. No, neither three pills nor two are going to do the job.

The killer ends up being a pregnant young woman who stole Mom's pill from the idiot who first stole it (apparently she too recognized a pill that hadn't been made in her lifetime) and used it to disable the victim, another young woman (5) by luring her into the water and holding her head under. Once again, pharmaceutically improbable; the pill hit immediately when the victim entered the water, enabling the pregnant killer to hold her head underwater. I'm not sure how this is possible because the petite killer looked like she couldn't hold a cabbage underwater.

Bottom line

This may be the first instance of a series that sucks both critically and pharmacologically! It's hard to tell which is more dated, the script or the choice of drugs. Either way, it's no better than a Lifetime Network movie and if you have a choice of watching this or staring at a toaster, choose the latter.

Or watch Shogun instead. I'm already hooked.

NOTES:

(1) Nembutal is no longer made nor used in the US.

(2) The therapeutic index is the ratio of the effective dose divided by the toxic dose. The higher the number the better. 

(3) Marilyn Monroe committed suicide using Nembutal along with other drugs. 

(4) Sodium thiopental lasted longer than the others. It was still used in general anesthesia until propofol (approved in 1986) kicked it out of hospitals. Propofol has a far superior profile. It revolutionized general anesthesia. 

(5) The victim had also been drinking, which would potentiate the action of the pill. Details.