ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
A group of SEDATIVE drugs with similar chemical structure. The barbiturates comprise a class of compounds that are chemically derived from barbituric acid, which was first synthesized in 1864. All of these compounds (examples of which are PENTOBARBITAL, PHENOBARBITAL and THIOPENTAL) are potent sedative- HYPNOTIC (calming and sleepinducing) drugs. In medicine these drugs have been used extensively as intravenous general ANAESTHETICS, and also as ANTICONVULSANTS. Considerable differences exist between differ ent types of barbiturates (with slightly varying chemical structure) with regard to onset and duration of action. For example, with thiopental the patient may fall asleep within seconds of infusion, and wake up five minutes later. Pentobarbital on the other hand induces sleep within five minutes of administration and has effects which last for up to sixty minutes. Before the development of the BENZODIAZEPINE drugs, barbiturates were also used to treat ANXIETY and INSOMNIA. However, their narrow THERAPEUTIC INDEX renders them quite dangerous, and much safer drugs are now used for these purposes. Barbiturates also have high ABUSE POTENTIAL, and chronic use can result in physical dependence. It is believed that barbiturates increase inhibitory mechanisms of the brain by enhancing NEUROTRANSMISSION at inhibitory GABA RECEPTORS, and generally suppress neuronal excitability.
Barbiturates And Minor Tranquilizers
S.J. Mulé, Henry Brill in Chemical and Biological Aspects of Drug Dependence, 2019
Barbituric acid, like the monoureides, may be synthesized by a condensation of urea with malonic acid (see Figure 1).3 The hexahydro-pyrimidine nucleus of barbituric acid contains three carbonyl groups which are capable of undergoing tautomeric transformations and four labile hydrogen atoms which may be substituted with different groups. To obtain barbituric acids with central nervous system depressant effects, the two labile hydrogens at the number 5 carbon may be replaced with either a straight or branched alkyl chain, an allyl, phenyl, or heterocyclic group.1 Unlike the hydrogens at carbon number 5, the hydrogen atom at the number 1 nitrogen is substituted less readily.4-6 Therefore, if a 5-monosubstituted barbituric acid is exposed to an alkyl substitution reaction as illustrated in Figure 2, the labile hydrogen at carbon 5 would be replaced first.
Sedative/Hypnotics
Frank A. Barile in Barile’s Clinical Toxicology, 2019
Barbituric acid was first synthesized in 1864 by the German researcher Adolf von Baeyer by condensing urea with diethyl malonate. As such, barbiturates are malonylurea derivatives (diureides; Figure 13.1). The electronegative carbonyl carbons confer an acidic nature to the molecule, thus classifying them as weak acids. Allyl, alkyl, and allocyclic side chains determine their pharmacological classification.Structure of prototype barbiturate.
Synthesis and characterisation of thiobarbituric acid enamine derivatives, and evaluation of their α-glucosidase inhibitory and anti-glycation activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
M. Ali, Assem Barakat, Ayman El-Faham, Hessa H. Al-Rasheed, Kholoud Dahlous, Abdullah Mohammed Al-Majid, Anamika Sharma, Sammer Yousuf, Mehar Sanam, Zaheer Ul-Haq, M. Iqbal Choudhary, Beatriz G. de la Torre, Fernando Albericio
Barbituric acid (BA) derivatives have been reported to have potential anti-hypertensive13, anti-cancer14, anti-convulsant15, anti-inflammatory16, anti-psychotic17, and antitumor properties18–21. Recently, these derivatives have also been reported as anti-diabetic agents22. On the other hand, thiobarbituric acid (TBA) analogues has been described to exert anti-inflammatory16,23, immunotropic24, anticonvulsant25, and anti-hypnotic25,26, anti-neoplastic27, and antitumor activities28. De Belin et al.29 reported a number of TBA derivatives as inhibitors of hypoxia-inducible factor 1 (HIF-1). Recently, Barakat et al.30 described the synthesis of a new series of diethylammonium salts of aryl substituted TBA derivatives as α-glycosidase inhibitors. Therefore, given the relevance of TBA derivatives in medicinal chemistry, the design of new molecules containing the thiobarbituric moiety is an inspiring goal.
The effect of acidic beverage versus mineral water on the change in serum phenobarbital concentrations: a randomized clinical trial on children with seizure
Published in International Journal of Neuroscience, 2021
Morteza Tavasolizadeh, Kazem Hasanpour, Milad Nazarzadeh, Davood Mahdian, Omid Gholami
Phenobarbital, the eldest modern anti-epileptic medication discovered in 1912, is a derivation of barbituric acid that increase binding to inhibitory gamma-aminobutyric acid receptors. It also inhibits glutamate induced depolarizations and regulate chloride currents through receptor channels [1]. One of the most common antiepileptic drugs used in neonates and children is phenobarbital [2]. One of the most important determination for oral bioavailability of drugs is absorption [3] and Phenobarbital has a weak acidity nature (pH at which the drug is 50% ionized (pKa) = 7.3). Absorption of a drug is influenced by the ionization state of drug, and ionization process is depends on the pH of the environment [4]. In an unionized state, permeability through the lipid bilayers of the intestinal mucosa is higher [4]. Based on Henderson–Hasselbalch equation, weak acidic drugs are predominantly in the unionized state and will thereby permeate more readily [4]. Therefore, based on the previous pharmacokinetics evidence, we hypothesized that intake of Phenobarbital with an acidic beverage such as Orange juice may increase Phenobarbital oral absorption.
Xanthine oxidase inhibitors: patent landscape and clinical development (2015–2020)
Published in Expert Opinion on Therapeutic Patents, 2020
Jatinder Vir Singh, Preet Mohinder Singh Bedi, Harbinder Singh, Sahil Sharma
Marbarone (9) (Figure 3), a barbituric acid derivative with significant cytotoxic potential instead, also has serum UA reduction ability as a side effect. These findings inspired researchers to develop its novel derivatives of Marbarone for the chronic life-long disorder of UA metabolism without any cytotoxic potential. Warrell research group is continuously working on barbiturates and has published many patents. In 2015, they claimed Marbarone derivatives 10 and 11 possessing XO inhibitory potential better than Allopurinol with the IC50 values of 1.06 and 0.68 µM, respectively (Figure 3). An important and valuable feature of these molecules is, they do not have any cytotoxicity if intended to use in a subject for a longer period of time. Additionally, the compounds also have the ability to excrete out the extra deposited UA from the body by inhibiting URAT1 enzyme (an enzyme that helps to reabsorb the UA from distal tubule). These were noteworthy findings that barbiturate derivatives can exhibit bifunctional activity, i.e. XO and URAT1 inhibition which could lead to the discovery of significantly potent antihyperuricemic drug after further development [86].
Related Knowledge Centers
- Alloxan
- Hydrogen Cyanide
- Hydrogen Iodide
- Organic Compound
- Pyrimidine
- Urea
- Uric Acid
- Barbiturate
- Malonic Acid
- Diethyl Malonate