Functional characterisation of the GABAA receptors
Adam Doble, Ian L Martin, David Nutt in Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
The β-carboline series have also been studied with regard to their efficacy at distinct receptor subtypes. Abecarnil is a full agonist at a1 and α3 containing receptors but a partial agonist at those which comprise α2 or α5 in combination with γ2 and a β subunit (Knoflach et al, 1993). However, while DMCM and βCCM exhibit clear inverse agonist activity at α1β1γ2 receptors, at α1β1γ2 receptors they are efficacious agonists (Puia et al, 1991). Interestingly, DMCM displays inverse agonist activity at α4β1γ2 receptors, although with rather less efficacy than at α1 containing receptors, while the partial agonists bretazenil and FG 8205 also retain their efficacy at this receptor subtype indicating that certain benzodiazepine site ligands will recognize α4 containing subtypes (Puia et al, 1992; Wafford et al, 1996).
Medicinal Plants: A Potent Antimicrobial Source and An Alternative to Combat Antibiotic Resistance
Jayanta Kumar Patra, Gitishree Das, Sanjeet Kumar, Hrudayanath Thatoi in Ethnopharmacology and Biodiversity of Medicinal Plants, 2019
Alkaloids diverse and abundant class secondary metabolites found at 10–15% concentration in almost all plants. Alkaloids are chemical compound containing basic nitrogen atom. They are colorless crystals. Their chemical structure is enormously dynamic. They are produced by wide variety of organisms such as plants, bacteria, fungus, etc. Many alkaloids have physiological effect that renders them valuable medicine against diseases like malaria, diabetics, cancer, and cardiac dysfunction. These are also practiced in local anesthesia and as analgesic compounds. The first example of alkaloid used in medicine was morphine isolated from Papaver somniferum. Morphine blunts the pain response secondary to the ischemic tissue damage along with providing anxiolysis. Codeine another alkaloid obtained from Papaver somniferum is a mild pain reliever and an effective cough suppressant. A number of alkaloids are being used as drugs for century. Among the oldest and best known of these is quinine, derived from the bark of the tropical cinchona tree which is used as an antimalarial drug. Berberine is another common example of alkaloid effective against Plasmodia and Trypanosomes. Mostly they control microbial regulation (Cowan, 1999). Harmine, a beta-carboline alkaloid, is widely distributed in the plants. Harmine has various types of pharmacological activities such as antimicrobial, antifungal, antitumor, cytotoxic, antiplasmodial, antioxidant, antimutagenic, antigenotoxic, and anti-HIV (Patel et al., 2012).
The Relaxation System Theoretical Construct
Len Wisneski in The Scientific Basis of Integrative Health, 2017
In 1977, when Dr. Claus Braestrup from Denmark located the benzodiazepine receptor, he did so by locating a compound, called β-carboline-3-carboxylic acid, in the urine of mentally ill patients. It was soon learned that β-carboline inhibits brain benzodiazepine receptors, and there was much speculation that some derivative of it might be an endogenous ligand for the benzodiazepine receptor (Braestrup et al., 1980). β-Carboline actually has a higher affinity for the benzodiazepine receptor than do most benzodiazepines. The only problem is that the molecule that Braestrup found was not really an endogenous ligand, but an artifact of the extraction process he used to isolate it. No matter, because it turned out to be profoundly useful anyway, and soon endogenous β-carboline alkaloids were located and found to be benzodiazepine ligands (Rommelspacher et al., 1981). These alkaloids (primarily harmane and norharmane) were also shown to possess antioxidant properties (Tse et al., 1991). At first, β-carboline was recognized as an antagonist (Beer et al., 1978). However, further testing uncovered its reverse agonist properties, that is, β-carboline can in fact produce anxiety and convulsions in animals and humans (Dorow et al., 1983; Duka et al., 1987; File et al., 1985; Rommelspacher et al., 1981). Because β-carboline does not share a recognition site with diazepam, researchers very early on began to speculate that the benzodiazepine receptor must be a multicomponent complex (Hirsch, 1982). In other words, it was clear that the benzodiazepine receptor site permitted numerous, diverse types of actions at its portal.
Small molecule and peptide-based CXCR4 modulators as therapeutic agents. A patent review for the period from 2010 to 2018
Published in Expert Opinion on Therapeutic Patents, 2020
Yesim A Tahirovic, Sameshnee Pelly, Edgars Jecs, Eric J Miller, Savita K Sharma, Dennis C Liotta, Lawrence J Wilson
In a US application (US20130172330), Altiris Therapeutics describes second generation analogs of AMD11070, with both bi and tricyclic heterocycles in place of the benzimidazole unit are described (18) [54]. This disclosure describes 27 synthetic procedures as well as 6 assays, which include calcium mobilization, impedance (cell wall morphology), anti-HIV entry, 125I-CXCL12 binding displacement, cytotoxicity and hERG channel binding. The activity of 33 compounds in on-target assays indicate that IC50 values vary from 10 nM to greater than 10 μM. There are 24 claims listing 179 distinct compounds with utility against over 25 types of cancer. The majority of the compounds in both the claims and assay results contain an N-substituted beta-carboline moiety. A subsequent publication describes mobilization of CD34+ HSCs in mice, measuring increases in CD34+ HSCs of four coded compounds, one of which corresponds to a structure in their patent application (19, Compound ID: ALT-1128) [55].
Putative mechanism for cancer suppression by PLGA nanoparticles loaded with Peganum harmala smoke extract
Published in Journal of Microencapsulation, 2021
Hoda Shabestarian, Masoud Homayouni Tabrizi, Monireh Movahedi, Ali Neamati, Fariba Sharifnia
Nowadays, many traditional medicines are enjoying a wide acceptance by the general public and continue to be used in their original form, including that of smoke. Among these medicinal smokes is the smoke from burning harmala seeds (Moloudizargari et al.2013, Shafiee and Moravej-Salehi 2015). Indigenous to Iran, harmala is a persistent, hairless plant, scientifically known as Peganum harmala from the Zygophyllaceae family (Abbott et al.2008, Marwat and Ur Rehman 2011). The active ingredients of Peganum include alkaloids that accumulate in its seeds and roots. These compounds are beta-carbolines, such as harmaline, harmine, harmalol, harman, and quinazoline, and their derivatives, such as vasicine and deoxyvasicinone (Kartal et al.2003, Passos and Mironidou-Tzouveleki 2016). In terms of temperament, harmala is warm and dry and has various properties characterised as hypnotic, antiperspirant, anti-cancer, anti-fungal, anti-bacterial, and anti-inflammatory (Lamchouri 2014).
Ayahuasca, a potentially rapid acting antidepressant: focus on safety and tolerability
Published in Expert Opinion on Drug Safety, 2022
Giordano Novak Rossi, Isabella Caroline da Silva Dias, Glen Baker, José Carlos Bouso Saiz, Serdar M. Dursun, Jaime E. C. Hallak, Rafael G. Dos Santos
As with every medicine, the quantity and proportion of DMT and beta-carbolines in ayahuasca must have an ideal dosage that maximizes the therapeutic effects while having the least amount possible of occurrence of AEs. To the best of our knowledge, there is still no published research in this regard. What is the minimum amount of beta-carbolines to make DMT orally active? What is the point where adding more beta-carbolines does not increase the length of effects of a fixed amount of DMT? Is it possible to utilize only one of them (harmine for example, which is the most studied) and reach the same effects? Would there be any advantages in terms of production costs, reductions of AEs, or any other benefits in doing so? Is it possible to use a DMT delivery method that allows it to bypass gastric MAO and reach systemic circulation without concomitant MAO inhibitors? These and many other questions regarding the use of these alkaloids have yet to be scientifically addressed. The biggest obstacles to overcome in this regard are related to the legal aspects of possessing the alkaloids (especially for DMT which is a scheduled substance in many countries) and the cultural heritage linked to ayahuasca use. Regarding the first obstacle, we as a global society seem to be going in the right direction with research on ayahuasca, psilocybin and other psychedelics advances. Considering the need for novel treatments for many mental disorders, as the therapeutic effects of these substances are unveiled, society may become more accepting of their medicinal use, to the point where they will become legal and maybe even commonly prescribed treatments. At that point, the stigma associated with their use will have subsided. Researchers from this area have the responsibility of doing things the right way so as to not let the events that happened in the first wave of psychedelic research decades ago be repeated in this new wave of research.