Levofenfluramine, or -3-trifluoromethyl-N-ethylamphetamine known as -fenfluramine or -fenfluramine, is a drug of the amphetamine family that, was never marketed. It is the levorotatory enantiomer of fenfluramine, the racemic form of the compound, whereas the dextrorotatory enantiomer is dexfenfluramine. Both fenfluramine and dexfenfluramine are anorectic agents that have been used clinically in the treatment of obesity. However, they have since been discontinued due to reports of causing cardiovascular conditions such as valvular heart disease and pulmonary hypertension, adverse effects that are to be caused by excessive stimulation of 5-HT2B receptors expressed on heart valves. Dexfenfluramine is believed to be responsible for the appetite suppressant properties of fenfluramine, of which it has been demonstrated to mediate predominantly via activation of postsynaptic 5-HT1B and 5-HT2C receptors through a combination of indirect serotonin releasing agent and direct serotonin receptor agonist activities.
Contrarily, levofenfluramine is thought to contribute only to unwanted side effects. Paradoxically, however, it has been shown that levofenfluramine too acts as a potent releaser of serotonin, though with 1/3rd of the efficacy of dexfenfluramine, As such, it would be expected to possess some degree of appetite suppressant properties as well, yet it does not. A potential explanation as to why levofenfluramine is not an effective anorectic is that it has been found to behave as a dopamine receptor antagonist, which, as dopamine antagonists like atypical antipsychotics are associated with causing increased appetite and weight gain—effects that their actions on dopamine receptors have been implicated in playing a role in the development of, is an action that could in theory cancel out the hypothetical serotonergically-mediated appetite suppressant effects of the compound. However, this has not been proven. Levonorfenfluramine, an active metabolite of levofenfluramine, is a potent serotonin releasing agent and to dexnorfenfluramine, is a 5-HT2B and 5-HT2C receptor agonist, as well as a somewhat less potent norepinephrine reuptake inhibitor.
As such contributes to the biological activity—though not appetite suppressant effects—of not only levofenfluramine but of racemic fenfluramine as well. In contrast to levonorfenfluramine, levofenfluramine is inactive as a reuptake inhibitor or releaser of norepinephrine, neither compound has any effect on dopamine reuptake or release. Fenfluramine Dexfenfluramine Norfenfluramine
The Shivering Truth is an American stop-motion animated surrealist anthology television series created by Vernon Chatman and directed by Chatman and Cat Solen. The show is produced by Solen with PFFR and ShadowMachine, features the voice talents of Chatman, Kevin Breznahan, Janeane Garofalo, Trey Parker, Miriam Tolan, Michael Cera, Jonah Hill, Starlee Kine; the Shivering Truth premiered at midnight on December 9, 2018 on Adult Swim, with the pilot episode having been released online on May 22, 2018 on the Adult Swim website. On November 7, 2019, Adult Swim announced that the show has been renewed for a second season set to debut in 2020; when announced in a press release by Adult Swim in May 2017, The Shivering Truth is described as "a delicately crafted, darkly surreal anthology comedy, a miniature propulsive omnibus cluster bomb of painfully riotous daymares all dripping with the orange goo of dream logic. A series of loosely-linked emotional parables about stories within tales that crawled out of the deepest caverns of your unconscious mind and became lovingly animated in breath-slapping stop motion – in other words, it is the TRUTH".
The characters in the show are 10-inch puppets with wire-based armatures, created with silicon, wool and resin. Chatman stated that around six months of physical production, a month of recording, two-and-a-half months of post-production were needed to complete six episodes. Chatman has noted several inspirations for his work on the show, including Terry Gilliam's work on Monty Python's Flying Circus, stating that "I saw it when I was young, so it scared me. I didn't know when the animation was beginning or ending." He explained that "A lot of my influences are non-animated in short films, novels radio shows. A recent one is David Eagleman's books on the brain. He's a neuroscientist and he gives you 40 different versions of the afterlife, none of them can co-exist." Solen has spoken on her inspirations as well, saying that "I loved the movie The Wizard of Speed and Time, a cautionary tale about making movies. Another film that I loved as kid was Nicolas Roeg's adaptation of Roald Dahl's The Witches, which featured both Anjelica Huston and Jim Henson's puppets.
It scared me so much!" The pilot episode premiered on the Adult Swim website on May 22, 2018. Before the television premiere at midnight on December 9, 2018, Adult Swim created an "online scavenger hunt" by releasing all six episodes on multiple websites and platforms. Daniel Kurland of Den of Geek praised the pilot along with the subsequent first episodes to premiere, giving the show a score of 5/5 and calling it "straight up one of the best things that I’ve seen in my life". Jonathan Barkan of Dread Central called the show "pure nightmare fuel genius", writing that it "looks like the cast aside baby of Charlie Kaufman and Wes Anderson... it's packed full of absurdist humor, the kind of stuff that you will watch and not be sure if you should laugh, wince, or look at your friends and ask,'What the fuck?'" Dave Trumbore of Collider wrote that "It’s not you get to put this level of artistry and insanity on display on an international television network", that "You’ll laugh while watching The Shivering Truth, but there’s just as good a chance that you’ll throw up a bit, too".
Jam, a similar comedy-horror sketch series Official website The Shivering Truth on IMDb
The Scottish National Party depute leadership election ran from 18 May to 8 June 2018. The election was contested for the party's new depute leader following the resignation of Angus Robertson in February 2018, after he lost his Westminster seat in the 2017 snap election. Keith Brown was announced as the winner of the election on 8 June 2018. Ballots opened on 18 May; the winner was announced as Keith Brown at the SNP conference in Aberdeen on 8 June. Nominations closed on 13 April 2018, there were three candidates: Keith Brown Member of the Scottish Parliament for Clackmannanshire and Dunblane and Cabinet Secretary for Economy and Fair Work Julie Hepburn, the only candidate, not an elected representative Chris McEleny, a councillor who ran in the last depute leadership election James Dornan, Member of the Scottish Parliament for Glasgow Cathcart who withdrew his candidacy on 8 April, he threw his support behind candidate Julie Hepburn. Pete Wishart Joanna Cherry Tommy Sheppard Ian Blackford Philippa Whitford The status of a second Scottish independence referendum was considered as a significant issue surrounding the depute leadership election, with Chris McEleny and Julie Hepburn seen as supporters of such a referendum occurring earlier rather than later.
Clare Adamson Ash Denham Annabelle Ewing Margaret Ferrier Ben MacPherson Ivan McKee Gil Paterson Humza Yousaf Angus McNeil Aileen Campbell James Dornan Bob Doris Fulton MacGregor Gillian Martin Alison Thewliss Kirsten Oswald Sandra White The depute leadership election was conducted using the single transferable vote system, with the results being declared on 8 June. Keith Brown was elected as the new Depute Leader of the Scottish National Party with a majority of 55.2% of votes cast in the second round of voting, beating rival candidate Julie Hepburn who secured 44.8%. Candidate Chris McEleny finished third with 16.2%, having been eliminated in the first round of voting. Nominations close in SNP deputy leadership race. BBC NEWS. Published 13 April 2018