Recent pharmacological developments in β-carboline alkaloid “harmaline”

Cannabinoid receptor agonism suppresses tremor, cognition disturbances and anxiety-like behaviors in a rat model of essential tremor

“…CB 1 receptors are presynaptically located where activation reduces presynaptic neuronal excitability and so inhibits neurotransmitter release (Howard et al , 2013). CB 1 receptor expression is abundant in several brain regions including the hippocampus, prefrontal cortex, nucleus accumbens and amygdala where their modulation of neurotransmitter release exerts a variety of behavioral and cognitive effects (Khan, Maalik, 2013). Here, a substantial body of evidence from animal models and human studies has shown that CB 1 receptor agonists, frequently in the form of ∆ 9 -tetrahydrocannabinol which is the principal psychoactive component derived from Cannabis sativa, induce numerous and complex effects on cognitive functions including attention, learning, emotional reactivity, enhancement of the perceptions of the senses, and, idiosyncratically, impairment and improvement in short-term memory (Barzegar et al , 2015, Razavinasab et al , 2013, Shabani et al , 2009, Shabani et al , 2011.…”

“…Systemic harmaline administration causes action tremor in mammals and has proved to be a useful animal model for the discovery of new therapies for primary symptoms of ET (Clifford, 1983a). Furthermore, in addition to harmaline causing agitation, cytotoxicity, delirium, paralysis, loss of coordination, tremor, visual disturbances and hallucinations (Khan et al , 2013), it has also been reported to induce cognitive disturbances, most likely as sequelae to low harmaline doses (5-10 mg/kg) acting anxiogenically or higher doses (20 mg/kg) exerting reportedly anxiolytic effects in rodents (Hilber and Chapillon, 2005). It has also reportedly affected emotional reactivity in mice as decision making in an anxiogenic situation can be altered by harmaline treatment (Hilber and Chapillon, 2005) in addition to inducing cognitive disturbances that manifest as motor and spatial learning impairments (Hilber and Chapillon, 2005).…”

Interaction of β-Carbolines with DNA: Spectroscopic Studies, Correlation with Biological Activity and Molecular Docking

“…1 Studies demonstrate that these alkaloids have several pharmacological actions, among them, anticonvulsant, anti-viral, antitumor, anti-proliferative and anti-microbial activity. [1][2][3][4][5] Moreover, β-carbolines act as deoxyribonucleic acid (DNA) intercalating agents and are able to inhibit the topoisomerases I and II enzymes, [6][7][8] which are responsible for regulating processes such as transcription, replication and DNA recombination. 9,10 Due to different activities demonstrated by this class of compounds, we have synthesized and evaluated the biological activities of several derivatives with different substituents at positions 1 and 3 of the β-carboline nucleus.…”

Indium‐Mediated Domino Allylation‐Lactonisation Approach: Diastereoselective Synthesis of β‐Carboline C‐3 Tethered α‐Methylene γ‐Butyrolactones

“…Accordingly, diversely substituted cinnamyl bromides (A-H) were treated with 1-(4-bromophenyl)-9H-pyrido [3,4-b]indole-3-carbaldehyde (5b) in presence of indium in anhydrous THF under refluxing at 80 o C. It is worthwhile to note that all the substrates smoothly afforded the desired products (6bA-bH) through clean reactions within 2-3 h in 56-82% yield after short silica gel column chromatographic purification (Scheme 4). Interestingly, no additive (p-TSA, TFA, TfOH, HCl, In(OTf) 3 ,NH 4 Cl, Yb(OTf) 3 , K 2 HPO 4 , K 2 CO 3 etc) was required for this transformation as compared to previous findings. [11] It was observed that the reaction of cinnamyl bromides (A-C, F-H) having electron withdrawing substituents was relatively faster and more efficient (68-82%) than D-E containing electron rich substituents, (56-64%).…”