Nom de Plume
Bluelighter
If I sound like an idiot, please, I implore you: don't scold me for it. Not that I'm easily offended or insulted—I couldn't be less emotional than if I tried. Aspergers, alexithymia, some neurodevelopmental pathology—call it what you may. But if ever I sound foolish or uncouth, it helps no one to jeer at and scold me. It's not of any utility. Teach me, like a mature adult , where I went astray or how my logic mislead me. Then, I'll be less foolish in the future. Banter only serves a single purpose if the object of the joke is not a willful participant in it: humiliation, shame, ridicule, mockery, derision, etc.
Besides I probably have a higher IQ than the overwhelming majority of everone of you. Yet, I feel inane, puerile jokes and teasing is too far beneath me to abase any one of your for your inferior intellect and arrant hebetude. Because IQ is not something one deserves to be praised nor castigated for. There are many facets to everyone, and no one is perfect. I don't get these jokes and thus these all make me defensive. May we now proceed with a mature dialectic?
I do struggle with humor, and I must say I find the inclusion of the word 'kidding' laudable and respectful. However, the risible aspect of this ungrammatical joke eludes me. So, kidding or otherwise, the expression is sans meaning, since language and its interpretation is always contingent on the foreknowledge of the audience. The word "dexterity" means nil to a monolingual Francophone.
Thank you for providing me with the correct nomenclature. I appreciate it.
Millions? Surely, that's hyperbole. The omphalos of my question was, in essence, why there are fewer of them (lysergamides) than, say, cathinones, amphetamines, or even other families of serotonergic psychedelics.
This doesn't seem like an adequate explanation. You're apparently saying the receptors—serotonin receptors, particularly the 5-HTa2 receptor)—is to blame for the veritable paucity of lysergamides. But there are thousands of other serotonergic compounds that this receptor permits. It seems there is no end of substituted amphetamines, cathinones, methylenedioxymethylamphetamines, tryptamines, phenethylamines, and a sundry other at least modestly serotonergic compounds that have been developed.
Yet, I am to accept without any incredulity the notion that serotonin receptors specifically discriminate against lysergamides whilst concomitantly being so incredibly permissive of nearly every other major set of serotonergic psychedelics and psychostimulants and entactogens?
If that is the case, then my concern is why and wherefore must it be? What is so repellent about lysergamides in particular?
Lets suppose a chemist—we'll christen Raj, for the sake of illustration—is working away arduously in his laboratory, fastidiously devising two compounds: a lysergamide or LSD agnate and an empathogen or MDMA agnate. Raj succeeds! He has produced these two novel compounds successfully. Now, let's suppose further that Raj is preparing to bioassay these two drugs in mice, so as to determine each of their serotonergic puissance, so to say.
The probability of Raj's empathogen display serotonergic pharmacodynamic properties is as likely as Raj's lysergamide not showing these properties,it patently appears.
So then, I ask: why are functional lysergamides as rare or rarer than non-functional derivatives of other families of serotonergics? What's so molecularly anomalous about these ergotamine-derived drugs?
The success rate of non-lysergamide compound, P, is apparently very similar to the failure rate of a lysergamide compound, Q.
Explain.
When we consider that novel compounds are almost never first bioassayed in human subjects, this quote suddenly becomes a meaningless non sequitur.
The pharmacologic unpredictability of an incipient compound is the reason why drugs are normally assayed first in non-human animal subjects, such as rodents or monkeys.
Moreover, when has this fear of unpredictability ever stifled scientific research into drug design or development? Is this yet one more distinguishing feature of lysergamides not applicable to other psychotropic compounds of scientific investigation?
If so, I ask again: wherefore?
1.) But Shulgin arguably did take many risks.
2.) You've failed to account for that utterly different, more brilliant creature: David Nichols. He is a man who can afford (through government funding) risks; has a more sophisticated laboratory and an entire staff of chemists at his disposal, so when risks arise they are promptly dealt with and eliminated; and Nichols is disparate from Shulgin yet further in that he also has access to laboratory test animals, namely lab mice, that he tests all his compounds on. Moreover, I'm not even sure D. Nichols has ever self-assayed his compounds. There is no evidence to corroborate that he does, did, will do, or even contemplated doing so. Therefore, all your enumerated justifications are nullified when we consider this crucial aspect.
You previous asseverated that no definitive or reliable (after an unspecified point) pharmacological assessment can be performed on a drug via solely it's molecular profile. Yet you're now doing an about-face and asserting the obverse. Which is it?
Moreover, pharmaceutical companies are not Gods of medicinal chemistry. Their employees nothing I'd presume any chemistry professional wouldn't know. The only disparity is in the technological and monetary advantages the pharmaceutical companies' staff have over the lone researcher with a chemistry PHd.
But you don't need hoards of cash nor state-of-the-art technology to make an educated guess as to what this or that molecular modification results in. All one needs is a model of the molecular structure (available from Wikipedia), the erudition and knowledge to know what substitutions can be performed and how, and a simple lab setup (if William Leonard Pickard can manage it, I'm sure some hypothetical Dr. Chemist would find it a veritable cinch), and the ability to conduct the desired synthesis (which was learned in grad school, presumably).
All the world's drugs are not shat out of the pharmaceutical industry. Most of them—remember those things called designer drugs—are the results of motivated and determined individuals, not multi-billion dollar corporations that care not for anything other serotonin, dopamine, norepinephrine, etc., reuptake inhibitors and antagonists—the marketing and sales of which account for almost half their total proceeds globally, per annum.
Besides I probably have a higher IQ than the overwhelming majority of everone of you. Yet, I feel inane, puerile jokes and teasing is too far beneath me to abase any one of your for your inferior intellect and arrant hebetude. Because IQ is not something one deserves to be praised nor castigated for. There are many facets to everyone, and no one is perfect. I don't get these jokes and thus these all make me defensive. May we now proceed with a mature dialectic?
I do struggle with humor, and I must say I find the inclusion of the word 'kidding' laudable and respectful. However, the risible aspect of this ungrammatical joke eludes me. So, kidding or otherwise, the expression is sans meaning, since language and its interpretation is always contingent on the foreknowledge of the audience. The word "dexterity" means nil to a monolingual Francophone.
Thank you for providing me with the correct nomenclature. I appreciate it.
Millions? Surely, that's hyperbole. The omphalos of my question was, in essence, why there are fewer of them (lysergamides) than, say, cathinones, amphetamines, or even other families of serotonergic psychedelics.
This doesn't seem like an adequate explanation. You're apparently saying the receptors—serotonin receptors, particularly the 5-HTa2 receptor)—is to blame for the veritable paucity of lysergamides. But there are thousands of other serotonergic compounds that this receptor permits. It seems there is no end of substituted amphetamines, cathinones, methylenedioxymethylamphetamines, tryptamines, phenethylamines, and a sundry other at least modestly serotonergic compounds that have been developed.
Yet, I am to accept without any incredulity the notion that serotonin receptors specifically discriminate against lysergamides whilst concomitantly being so incredibly permissive of nearly every other major set of serotonergic psychedelics and psychostimulants and entactogens?
If that is the case, then my concern is why and wherefore must it be? What is so repellent about lysergamides in particular?
Lets suppose a chemist—we'll christen Raj, for the sake of illustration—is working away arduously in his laboratory, fastidiously devising two compounds: a lysergamide or LSD agnate and an empathogen or MDMA agnate. Raj succeeds! He has produced these two novel compounds successfully. Now, let's suppose further that Raj is preparing to bioassay these two drugs in mice, so as to determine each of their serotonergic puissance, so to say.
The probability of Raj's empathogen display serotonergic pharmacodynamic properties is as likely as Raj's lysergamide not showing these properties,it patently appears.
So then, I ask: why are functional lysergamides as rare or rarer than non-functional derivatives of other families of serotonergics? What's so molecularly anomalous about these ergotamine-derived drugs?
The success rate of non-lysergamide compound, P, is apparently very similar to the failure rate of a lysergamide compound, Q.
Explain.
When we consider that novel compounds are almost never first bioassayed in human subjects, this quote suddenly becomes a meaningless non sequitur.
The pharmacologic unpredictability of an incipient compound is the reason why drugs are normally assayed first in non-human animal subjects, such as rodents or monkeys.
Moreover, when has this fear of unpredictability ever stifled scientific research into drug design or development? Is this yet one more distinguishing feature of lysergamides not applicable to other psychotropic compounds of scientific investigation?
If so, I ask again: wherefore?
1.) But Shulgin arguably did take many risks.
2.) You've failed to account for that utterly different, more brilliant creature: David Nichols. He is a man who can afford (through government funding) risks; has a more sophisticated laboratory and an entire staff of chemists at his disposal, so when risks arise they are promptly dealt with and eliminated; and Nichols is disparate from Shulgin yet further in that he also has access to laboratory test animals, namely lab mice, that he tests all his compounds on. Moreover, I'm not even sure D. Nichols has ever self-assayed his compounds. There is no evidence to corroborate that he does, did, will do, or even contemplated doing so. Therefore, all your enumerated justifications are nullified when we consider this crucial aspect.
You previous asseverated that no definitive or reliable (after an unspecified point) pharmacological assessment can be performed on a drug via solely it's molecular profile. Yet you're now doing an about-face and asserting the obverse. Which is it?
Moreover, pharmaceutical companies are not Gods of medicinal chemistry. Their employees nothing I'd presume any chemistry professional wouldn't know. The only disparity is in the technological and monetary advantages the pharmaceutical companies' staff have over the lone researcher with a chemistry PHd.
But you don't need hoards of cash nor state-of-the-art technology to make an educated guess as to what this or that molecular modification results in. All one needs is a model of the molecular structure (available from Wikipedia), the erudition and knowledge to know what substitutions can be performed and how, and a simple lab setup (if William Leonard Pickard can manage it, I'm sure some hypothetical Dr. Chemist would find it a veritable cinch), and the ability to conduct the desired synthesis (which was learned in grad school, presumably).
All the world's drugs are not shat out of the pharmaceutical industry. Most of them—remember those things called designer drugs—are the results of motivated and determined individuals, not multi-billion dollar corporations that care not for anything other serotonin, dopamine, norepinephrine, etc., reuptake inhibitors and antagonists—the marketing and sales of which account for almost half their total proceeds globally, per annum.
