What Neurobiology Has to Say About Why People Abuse Alcohol and Other Drugs
Richard T. Spence, Diana M. DiNitto, Shulamith Lala Ashenberg Straussner in Neurobiology of Addictions, 2014
The fact that some individuals develop a compulsive drug use pattern in response to emotional pain cannot be denied. In the case of alcoholism, about 5-10% of those who are alcohol dependent can be labeled as having primary depression with secondary alcoholism. For these individuals, depression preceded their alcoholism. It is likely that these individuals began using alcohol to attenuate their negative moods. However, they are less likely to have a family history of alcoholism than primary alcoholics (Littrell, 1991a), and, thus, their alcoholism is less likely to be genetically based. Additionally, women, for whom the case for inherited alcoholism is less well established, are more likely to display this form of alcoholism (Littrell, 1991a; 1991b). In contrast, about 85% of alcoholics are high scorers on the MacAndrew scale, an MMPI scale whose items overlap with items on the Sensation Seeking Scale (Littrell, 1991a). They are more likely to be primary alcoholics for whom depression was not apparent prior to the inception of their drinking careers (Littrell, 1991a). Moving beyond alcohol to other drugs, sensation seeking is probably the strongest trait predictor of compulsive drug use (Sabol et al., 1999). Therefore, it is unlikely that primary alcoholics and sensation-seeking individuals began their drug use careers in order to medicate depression, because, as a group, they are less likely to be depressed.
Chemoenzymatic Approaches towards (S)-Duloxetine
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Nina Schneider et al. disclosed the synthesis of (S)-3-chloro-1-(thiophen-2-yl)-1-propanol 9a by application of recombinant Aromatoleum aromaticum. The phenylethanol dehydrogenase EbN1 from Azoarcus sp. (also known as Aromatoleum aromaticum) reduces the ketone viz. 3-chloro-1-(thiophen-2-yl)propan-1-one 7 to the respective alcohol viz. (S)-3-chloro-1-(thiophen-2-yl)propan-1-ol 9a. For this reaction, the dehydrogenase desired the co-factor nicotinamide-adenine dinucleotide (NADH), which forms the required reduction equivalents. This expensive co-factor can be regenerated with the assistance of a 2o “sacrificial alcohol” (such as 2-butanol or 2-propanol), during which the respective ketone (such as 2-butanone or acetone) is formed. Relatively long-chain alcohols are preferred by the enzyme here, but are also considerably more expensive. For this purpose, 2-butanol is employed as sacrificial alcohol (Scheme 5.12) (Schneider and Höffken, 2004). (S)-Duloxetine by recombinant Aromatoleum aromaticum.
Spray Drying and Pharmaceutical Applications
Dilip M. Parikh in Handbook of Pharmaceutical Granulation Technology, 2021
Closed-cycle layouts are mainly used for nonaqueous (i.e., organic solvents) feedstock and generally require the use of inert gas as the drying medium. This type of spray dryer is operating in gaseous nitrogen as an inert medium circulating in a closed cycle within all the equipment. As the feed medium from the feed pump is atomized by the rotary atomizer or a nozzle that forms a fine droplet of liquid particles, further heat from the heater vaporizes the liquid droplets to vapor phase and the product is left as powder form in the cyclone separator. The drying process can be adjusted by the temperature controller of the heater. The evaporation of the solvent is to be recovered through the condensation unit. The success of closed-cycle spray drying washing and cooling operation requirements will be part of accurate temperature control. For a high boiling point of alcohol generally cooling water or saltwater is employed, whereas for the low boiling point solvents, such as dichloromethane, hexane, and acetone, the refrigeration cycle is incorporated in the design [25].
Molecular mechanisms of ethanol biotransformation: enzymes of oxidative and nonoxidative metabolic pathways in human
Published in Xenobiotica, 2020
Grażyna Kubiak-Tomaszewska, Piotr Tomaszewski, Jan Pachecka, Marta Struga, Wioletta Olejarz, Magdalena Mielczarek-Puta, Grażyna Nowicka
Alcohol sulfotransferase is also capable of coupling both primary and secondary short-chain aliphatic alcohols, including ethanol, with sulfuric acid, with a much lower affinity to these substrates. Adenosine-3′-phospho-5′-phosphosulfate (phosphoadenosine-phosphosulfate, PAPS) is a donor of the sulfonate radical transferred to the oxygen of the hydroxyl group. In this way, small amounts of ethanol can be metabolized into ethyl sulfate (EtS), which is excreted in the urine (Figure 8). Since EtS is excreted in urine for a much longer period than ethanol (up to 48 hours after single consumption and up to 130 hours after prolonged intensive consumption and subsequent withdrawal of alcohol), it is used as a biomarker of intensive alcohol consumption. Moreover, significantly higher activity of sulfotransferases in foetuses compared to ADH suggests that it may be a metabolically important way of ethanol inactivation during prenatal development, as well as a maternal alcohol consumption indicator during pregnancy (ExPasy, 2020; Heier et al., 2016; IUBMB, 2020; Kurogi et al., 2012; Mitchell et al., 2014) (Table 5, Figure 13).
Intoxication with Fireball Whiskey causing severe lactic acidosis
Published in Baylor University Medical Center Proceedings, 2021
Moeed Ahmed, Sunil K. Jagadesh, Mohamad Ali Alhajhusain, Sangeeta Mutnuri
Propylene glycol is a viscous, colorless liquid that possesses a faintly sweet taste. Containing two alcohol groups, it is classified as a diol. It is miscible with a wide range of solvents, including water, acetone, and chloroform. It has been approved by the US Food and Drug Administration for use as a preservative in foods and as a solvent in pharmaceuticals.1 Unlike methanol and ethylene glycol (which cause high anion gap metabolic acidosis), it is not classified as a toxic alcohol. Cases of propylene glycol poisoning are usually related to either inappropriate intravenous administration or accidental ingestion of large quantities by children.2 Propylene glycol is also one of the ingredients used in Fireball Whiskey. We present two cases of severe lactic acidosis in the setting of Fireball Whiskey use.
Spectroscopic observations of β-eudesmol binding to human cytochrome P450 isoforms 3A4 and 1A2, but not to isoforms 2C9, 2C19, and 2D6
Published in Xenobiotica, 2022
Dawid Krenc, Kesara Na-Bangchang
BEU bound to CYP1A2 with an affinity comparable to that of CAF. The binding resulted in reverse type I difference spectra, similar to CAF. This spectral change reflects an increase in the coordinate bonding of water to Fe3+, which may be due to a displaced ‘endogenous ligand’ (Sandhu et al. 1994, Luthra et al. 2011). Substrates of CYP1A2 are likely to be planar molecules (Lewis and Ito 2010). Although it is not aromatic, the trans-fused double ring of BEU (strictly speaking, trans-BEU, see Varma et al. 1962) makes it a relatively planar molecule (Figure 1(B)). The ring-bound methyl group is arranged vertically to the plane. The hydroxyl group and its two neighbouring methyl groups may each be arranged vertically, depending on the rotation of the tertiary alcohol group. The similar spectral behaviour of BEU and CAF binding to CYP1A2 was remarkable (Figure 5(B)), especially since the former is at least 1000-fold less water-soluble than the latter.
Related Knowledge Centers
- Chemistry
- Ethanol
- Functional Group
- Methanol
- Organic Compound
- Sucrose
- Hydroxy Group
- Saturated & Unsaturated Compounds
- Cholesterol
- Salt-Effect Distillation