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  • Amir Muhaisen

Eye-Opener : Amir-Diol !!

in this article, effects of conventional ethanol-based alcoholic drinks are illustrated with an aim to develop an ethanol-free alternative with less hangout effects

amir-diol : ethanol-free-alcohol

Normally, alcoholic drinks are ethanol-based in which ethanol as an active ingredient contributes for psychoactive effects ; beer (5% ethanol) , wine (13% ethanol) , and hard liquor (40% ethanol). Therefore, what happens inside your body upon consumption is that ethanol flows down into stomach , moves down into small intestine , diffuses through epithelium membranes to reach bloodstream , distributes throughout brain , liver , kidneys , and lungs


Practically, ethanol content of standard hard liquor (40% ethanol , 43 ml) can be absorbed into blood within 30 minutes , not to mention that presence of fatty meals in stomach reduces blood alcohol concentration up to 50% relative to that when consumed on an empty stomach


In reference to psychoactive effects, ethanol affects brain functions via disruption of neural excitation and inhibition pattern that is essential for normal brain functions , hence ethanol increases inhibitory and decreases excitatory functions as potent depressant


Basically, ethanol mimics γ-amino butanoic acid , in which partially binds to γ-amino butanoic acid receptors , keeps channels open to allow chloride anions to flow into neuron to become less responsive thus increases inhibitory effect as sedation comes into effect , and further induces dopamine release , besides impaired body movements and slurred speech

gamma-aminobutanoic-acid-receptor , glutamic-receptor

Furthermore, ethanol reduces glutamate receptors permeability thus decreases excitatory functions not to mention that ethanol effects are directly related to the amount consumed


Note that liver breaks down most of ethanol you drink therefore to be removed from your body hece metabolism rate in the liver is approximately 6 ml ethanol per hour which varies from person to person upon genetic and environmental factors


Critical to mention, ethanol metabolism is based on enzymes ; alcohol de-hydrogenase (ADH) that converts ethanol into to acetaldehyde (alcohol → aldehyde) , and aldehyde de-hydrogenase (ALDH) that converts acetaldehyde into acetic acid (aldehyde → carboxylic acid) to be further excreted in urine in acetate form

ethanol-metabolism

In contrast, ethanol metabolims unintentionally creates more toxic chemicals in which acetaldehyde metabolite accounts for hangover


Chemical Analogues


Notice that ethanol metabolism resembles how liver breaks down primary alcohols via alcohol de-hydrogenase (ADH) and aldehyde de-hydrogenase (ALDH) as illsutrated

primary-alcohol : metabolism

Consequently, methanol is extremely toxic upon formation of metabolites ; formaldehyde and formic acid that produce optic nerve toxicity thus permenant blindness as reported in denatured alcohol consumption incidents


Keep in mind that n-propanol and n-butanol have similar psychoactive effects to ethanol, though n-propanol is 3 times potent than ethanol, and n-butanol is 6 times more potent. In other words, psychoactive effects upon consumption of conventional hard liquor drink (40% ethanol , 43 ml) is equivalent to (13% n-propanol , 43 ml) or (7% n-butanol , 43 ml) , yet both are commercially inconvenient because n-propanol and n-butanol prices are presently (+11%) and (+13%) compared to absolute ethanol not to mention cheaper bio-ethanol distillates compared to n-propanol and n-butanol value chain


On the other hand, secondary alcohols are turned into ketones, thus i-popanol metabolism via alcohol de-hydrogenase (ADH) produces acetone metabolite that is further converted into acetate and formate via an energy-intestive pathway that leads to hypoglycemia , important to mention here that i-propanol is also 3 times more potent than ethanol

secondary-alcohol : metabolism

In search for alternatives, diols or glycols such as ethylene glycol , propylene glycol , and butylene glycols to be evaluated as for psychoactive effects and metabolism


Therefore, ethylene glycol has negligible psycho-active effects compared to being extremely toxic upon formation of metabolites ; glycolaldehyde which is metabolized further into toxic glycolic acid , and oxalic acid that precipitates as insoluble oxalate crystals within brain , liver , and kidney tissues as reported in anti-freeze consumption incidents

ethylene-glycol : metabolism

Nevertheless, propylene glycol has negligible psycho-active effects yet less toxic upon formation of metabolites ; lactaldehyde which is metabolized into lactic acid and lactate in which consumption causes high metabolic anion gap and further implications

propylene-glycol : metabolism

Exceptionally, butylene glycols have intrigued researchers ; 1,3-butanediol metabolism via alcohol de-hydrogenase (ADH) produces 3-hydroxybutyrate and acetoacetate which are further used as energy-source in absence of sufficient blood glucose , hence positive effects includes body mass loss and slight psychoactive-effects compared to ethanol

butanediol : metabolism

Note that 1,3-butanediol has stereoisomers ; R-1,3-butanediol that undergoes full metabolism, and S-1,3-butanediol in which only 30% is converted into S-3-hydroxybutyrate upon possible stereospecificity


Another butylene glycol isomer have gained attention ; 1,4-butanediol metabolism via alcohol de-hydrogenase (ADH) produces 4-hydroxybutyraldehyde which is further converted via aldehyde de-hydrogenase (ALDH) and transaminase into γ-amino butanoic acid that fully binds to γ-amino butanoic acid receptors to increases inhibitory effect as well as sedation , hence rich psychoactive experience that includes dopamine release , euphoria , and enhanced sex-drive

butanediol : metabolism

Commercially, 1,4-butanediol have been promoted for body-builders upon claims that its metabolite enhance growth hormones and steroids effect, moreover as sleep-aid


Keep in mind that 1,4-butanediol psycho-active effect is of minor importance compared to its metabolite in which effects are dose-dependent


Consequently, psycho-active effects upon low-dose consumption (0.5 ml - 1.0 ml) are relaxation , sociability , and disinhibition as similar to moderate ethanol consumption yet more euphoric


In addition, psycho-active effects include noticable music enhancement as auditory stimuli enhance dopamine release , besides impaired body movements and slurred speech upon adequate dose (1.5 ml - 2.5 ml) which is somehow similar to excess ethanol consumption yet with enhanced libido-effect : sex-drive !!


Practically, psycho-active experience lasts for 3 hours while onset takes place after 15 mins, no hangovers as with ethanol-based alcohols


Note that metabolism of 1,4-butanediol is inhibited by ethanol, that's why co-consumption must be avoided


Furthermore, nausea and drowsiness followed by unconsciousness are symptoms of excessive dose (+2.5 ml) , while lethal dose (+7 ml) leads to convuslions, and respiratory depression as over-dose have been reported in recreational incidents, because accurate dosing is difficult for individuals, that's why formulated product is needed


Industrial Production

handbook for chemical engineers and entrepreneurs

Here you will find present-day industrial synthetic routes and simplified flow diagrams to further illustrate 1,4-butanediol production





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Commercial Approach


Recently, an emerging fitness supplement company provides 1,3 butanediol drinks which are branded as ethanol-free "ketogenic" alcohol in reference to 3-hydroxybutyrate and acetoacetate energy-rich metabolites that are also called ketone-bodies


However, marketing seems challenging as for less psychoactive-effects and high price compared to conventional ethanol-based drinks upon minimum-dose formulation , butylene glycols value chain , and stereoisomer purification since only R-1,3-butanediol is used in product formulation


Chemiprobe started “probing” for technical insights about 1,4-butanediol since last week , and continuously networking with professionals in alcoholic beverages and fancy drinks in an effort to develop an efficient formula for “Amir-Diol” that could be branded as the trail-blazer of ethanol-free “libido-enhancer" alcohol

amir-diol : ethanol-free-alcohol

In reference to formulation, an optimum concentration (0.18% 1,4-butanediol , 490 ml) for seltzer-based (pH 4.5) is safe since over-consumption means +7 drinks (3.4 liters) in a row to reach lethal limit that is further subdued thanks to over-hydration


Keep in mind that relaxation , sociability and libido-effects as for unique psychoactive experience with no-hangovers , will compensate for high price compared to conventional ethanol-based drinks , this is a luxury drink though !!



intestinal epithelium : dynamic lining of intestine , composed of single layer of cells that functions as physical barrier


neuron : nerve cell

neurotransmitter : chemicals secreted by neurons to induce excitatory or inhibitory fuctions

excitatory neuron : secrete excitatory neurotransmitters to stimulate other neurons

inhibitory neuron : secrete inhibitory neurotransmitters to supress responsiveness


depressant : exogenous or endogenous chemical that cause sedative effect


γ-amino butanoic acid : an inhibitory neurotransmitter , abbreviated as GABA


neuron excitability : electrical voltage across neuron's membrane

→ (+) more responssive

→ (-) less responsive


glutamate : an excitatory neurotransmitter


hangover : after-effects caused by drinking ethanol-based alcohol (headache)


olefins hydroformylation

ethylene → propionaldehyde → n-propanol

propylene → n- butyraldehyde → n-butanol


hypoglycemia : low blood sugar level


stereospecificity : reaction mechanism that operates on specific stereoisomer


seltzer : artificial carbonated water , soda water


Hard Ketones limited is an american fitness supplement company with specialty in butanediol drinks , headquartered and registered in Washington, D.C


References


1. McCarthy, C et al. (2021) “physiologic, metabolic, and toxicologic profile of 1,3-butanediol” Pharmacology Experimental Therapeutics, 379(3), pp. 245–252


2. Schep, L.J. et al. (2012) “clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol” Clinical Toxicology, 50(6), pp. 458–470


3. Wong, C. et al. (2004) “from street to Brain : neurobiology of recreational γ-hydroxybutyric acid” Trends in Pharmacological Sciences, 25(1), pp. 29–34.


4. Poldrugo, F. (1999) “review : role of gamma-hydroxybutyric acid in the treatment of alcoholism” Alcohol and Alcoholism, 34(1), pp. 15–24


5. Kam, P.C. Yung, F.F. (1998) “gamma-hydroxybutyric acid: an emerging recreational drug” Anaesthesia, 53(12), pp. 1195–1198

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