What is Esketamine?

You may have seen that an antidepressant called “Esketamine” has been approved for use in the UK. Sounds a bit like ketamine you’re thinking, and you’d be right. It is a purified form of the more well-known drug, commonly thought of as a horse tranquiliser and often used as a drug of abuse.

Many drug molecules come in two forms, what you might refer to as a left-handed and a right-handed form. When they are manufactured, both the left (known as the S) and the right (labelled R) form are produced, usually in equal quantities. Often one form, R or S is more active than the other, as is the case with the painkiller ibuprofen.

Sometimes, one form is active and the other form causes side effects. This is the case with thalidomide, although the forms are interconverted in the body so it is impossible to make a safe form of that particular drug for women who are or might get pregnant.

Standard manufacture of ketamine produces the R and the S form, (R,S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone. The R form, interacts with additional receptors in the body that are not the chosen target of the drug and so lead to side effects. Hence, the need to produce ketamine as the S form only for use in treating depression. The drug S-ketamine, thus becomes esketamine. The S form is twice as potent as the mixture of R and S. The R form is nominally arketamine, clever naming.

Esketamine is marketed as Ketanest and Spravato, commonly used as a general anesthetic (intravenous) and now for severe, treatment-resistant depression (nasal spray). The drug acts by blocking the NMDA (N-methyl-D-aspartate) receptor in the nervous system and also acts as dopamine reuptake inhibitor. Dopamine release is associated with pleasure and feelings of reward, these feelings can, theory goes, be made to last longer if the dopamine remains active and is not “reuptaken” back into nerve cells too quickly.

Ketamine can be addictive and so can its S enantiomer, esketamine, which as mentioned has now been approved in the UK. Some physicians are concerned about its use. Addictive nature aside, there is the issue that esketamine increases glucose metabolism in the frontal cortex of the brain and this may be responsible for the more psychologically dissociative and hallucinogenic effects of esketamine. Arketamine decreases glucose metabolism in the brain and is thus reportedly more relaxing.

On balance, the ratio of benefits to risk is considered high enough that it can be safely used for some patients with severe and very debilitating forms of depression.

Footnote

The one thing I’ve not yet ascertained is whether or not the manufacture of esketamine begins with the 50:50 racemic mixture of the R and S forms and involves their separation prior to formulation of esketamine or whether the manufacturer has an enantioselective synthetic route that gives them a bigger proportion of the S form and less waste when they remove the R form prior to formulation. Luddchem pointed out a cyclodextrin paper published by Wiley here.

The (New) Elements Song

I mentioned my friend Helen Arney‘s marvellous update of the classic chemical song by Tom Lehrer a while back (December 2016). Now, the team from the Royal Society of Chemistry’s Chemistry World magazine, led by another, Ben Valsler, have crowdsourced a choir to join Helen and Waterbeach Brass (the brass band from the village eastwards across the A10 road from us here in Cottenham) to record a new rendition as we come to the finale of the International Year of the Periodic Table. It’s super!

Science on TikTok

UPDATE: Well, it was worth a try…some of the vids I posted had a few hundred views and a handful of likes, one got 1500+ views and a few dozen likes. But the vast majority of the stuff on there is pointless nonsense and there seems to be little engagement to be frank. Even attempting to find STEM people has not really worked so far. I am going to leave it to brew on the backburner for a while over the Christmas period and come back to it next month.

You may have heard about TikTok, it’s a fairly new video platform (actually, it’s ancient, founded in September 2016!). Rumour has it that’s mostly youngster doing silly stunts and pranking each other and if it’s not that then its craftspeople and builders and decorators showing off their skills in plastering, bricklaying, tree-felling, carving, plastering, and other stuff. There’s been some 15-second activism that hit the headlines recently and seems to be growing…

I registered with the app soon after it launched, but never used it at the time. Well, as I mentioned here a few days ago I was inspired by engineer-inventor Dr Lucy Rogers to take a closer look as I imagined that there could be potential for engaging and perhaps even inspiring some of those youngsters with some sciencey videos.

My early postings are a bit eclectic, some music, some moths, a stylish stile, silly snowy filters, and others bits & bobs. Some seem to have been viewed several hundred times and liked by a few dozen users; others don’t seem to have hit the target at all.

Anyway, as I did with Twitter more than a decade ago, I thought it might be nice to start compiling a list of STEM people active on TikTok and maybe even encourage a few who aren’t but who have content that they share on other social media to take a look. So, I’ve made a start and will add anyone who is in STEM and sharing experiments, demos, and other pertinent stuff, just let me have your handle and I’ll take a look.

@sciencebase
@DrLucyRogers
@RuthAmos
@RobIves
@DavidDobrik
@ChemTeacherPhil
@Rahul
@InstituteofHumanAnatomy
@TheJKGamer1
@SarahMackAttack
@lab_shenanigans
@TheTikTokScientist

The International Space Station, ISS

I totally forgot that I’d had another got a photographing the International Space Station, ISS, as it flew overhead a few nights ago. The photos were not very good, so I headed outside to try and catch this evening’s very bright, overhead flypast and was a little more successful.

If it’s flying over where you live and it’s night time and the sky is clear, look to the western horizon for a steady, bright light that travels across the sky heading East, it will take several minutes to cross the sky, it moves quite quickly so hard to get a focus lock on with a big lens. There’s no twinkling, no flashing lights, just a very bright steady and steadfast light.

This was the best of a large sequence of photos I snapped where you can definitely see the shape of the beast and how it is rotating as it travels across the sky. Full-frame SLR with a 600mm zoom lens, EV turned down a few notches, ISO as low as I could go and get an exposure. f/5.6 but that’s irrelevant and a short shutterspeed to preclude shake while handholding the machine.

This is a 48×48 pixel crop from my original 5472×3648 photograph scaled up 4x and coupled with a NASA photo of the ISS so you can see better what it is you’re actually looking at here!

Below is a 768 pixelwidth crop of the original. The white speck in the middle is what I’ve cropped to in the view above

Spare a thought for our winter visitors

Many people are well aware that the British Isles welcomes a lot of summer visitors – the cuckoos, swifts, swallows, house martins, and many other migratory species that head north in the spring from their season in the sub-Saharan sun. But, there are also visitors in the winter, birds that head south from the cold to catch a little of the warmth of the Gulf Stream. As far as we know many birds adopted migratory behaviour in response to the Ice Age and having evolved to cope with that are locked into that pattern, at least until climate changes in a significant way once more.

Fieldfare

I wrote about a winter visitor that reaches our shores some time ago in this newsletter – the starlings. While we have lots of starlings all year round, those vast flocks we know as murmurations occur when the starling forces are bolstered by visitors. If you head out to the local nature reserves and even just the outskirts of the villages you are likely to see many other visitors among the flocks of gulls and crows, for instance. Among the grey and white clouds of the more well-known gulls, there might be something a little less common, an ivory gull for instance or perhaps even a glaucous gull and we did have a hooded crow on the outskirts of our village, Cottenham, last year.

Redwing

Among the other winter visitors that turn up in greater numbers are a couple of thrush-type species, related to the blackbird and the song thrush, namely the fieldfare and the redwing. Both species will make a winter home on farmland and use the hedgerows and bordering trees and woodland. Both eat a lot of berries and will attempt to out-compete the resident blackbirds and thrushes for supplies. Should the weather turn foul, as happened when we had the so-called “Beast from the East”.

These birds headed for the relative shelter of our gardens and began stripping firethorn and rowan trees of any remaining berries. Another reason not to be too tidy in pruning back your bushes in the autumn. Incidentally, there were still fieldfares to be seen in the trees that border the allotments and the recreation ground as recently as April, despite most winter visitors having departed for their northern summer homes.

waxwing benton 2 e1523904354898
Waxwing

Of course, having some vast wet spaces and in being so close to Norfolk, we have plenty of waterfowl visitors in winter – geese, ducks, swans. These head south from Scandinavia and elsewhere to take advantage of the relative warmth here when the chills really do set in up north. Many readers will no doubt have visited WWT Welney to see the large numbers of Whooper and Bewick’s swans and other waterfowl that arrive each autumn there.

Goldcrest

Among the less common birds you might see around the village and in local woodland that turn up for the winter are goldcrests. This species holds joint first place with the firecrest as our smallest bird species, far smaller than the resident wren, which is our most common resident. That said, you can see goldcrests and firecrests at any time of year.

Whooper Swan

Another relative rarity to watch out for, especially around trading estates and supermarket car parks where there are often lots of berry-laden trees is the waxwing. This elegant and bohemian species spends the summer in the far north, but is peripatetic, rather than migratory, in the winter, and often turns up unannounced in large flocks to those berry-rich sites when food is short in the north. Watch out for huddles of people in olive green and beige with thinly insulated hats hanging around The Beehive Centre or the guided busway parking areas with binoculars and ‘scopes pointing them hopefully at rowan trees and the like and you might just spot an elegant visitor.