Monoterpene Indole Alkaloids and Mental Health Ibogan-type alkaloids have been proposed as therapeutics for neurological and psychiatric disorders [1] and the parent molecule was once "sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market" Combinations of low doses ibogan-type alkaloids (0.01 − 2.0 mg/kg) and antidepressants are proposed to "produce a synergistic effect in reducing symptoms of psychiatric disorders such as bipolar disorder, depression, schizophrenia, paranoia, anxiety, panic disorder, mania, post-traumatic stress disorder (PTSD), and obsessive − compulsive disorder... [providing a] highly efficient therapeutic responses compared to when each of the active agents is used alone" Catharanthine from Catharanthus roseus and Tabernaemontana divicarta has been proposed to be a pharmacological treatment for addiction without the adverse side effects associated with ibogaine. It "slows DA reuptake and increases extracellular DA in the nucleus accumbens through partial inhibition of DATs" and potentiates GABAARs [2] The root alkaloids from C. roseus root seem to be potent AChE inhibitors and catharanthine exhibited nicotinic receptor antagonism Exploring a common Apocynaceae - Catharanthus roseus The cytotoxic vinca alkaloid constituents are only found in the aerial parts of Catharanthus roseus ( Figure 1 ), the roots are used in several countries as decocts or hot water extracts for 1 the treatment of a number of conditions The dried root is an industrial source of ajmalicine ( raubasine ), which increases the blood flow in the brain and peripheral parts of the body Preparations of it are used to treat the psychological and behavioural problems of senility , sensory problems ( dizziness , tinnitus ), cerebrovascular accidents , cranial traumas and their neurological sequelae In general , toxicity showed that both extracts and isolated compounds are safe to a certain limit , beyond that they cause adverse effects [ 1 ]. That said , the yield of vinblastine and vincristine from C roseus aerial parts is is low , whereas the precursors , catharanthine and vindoline , are present in higher concentrations [ 2 ]. In the stem , there was in micrograms per milligram fresh weight ( FW ): catharanthine , 0 506 ± 0 044 ; ajmalicine , 0 071 ± 0 022 ; serpentine , 0 397 ± 0 031 ; tabersonine , 0 017 ± 0 003 ; and vindoline , 0 0026 ± 0 0002 ( 0 5mg / g fresh weight catharanthine in stem ) Figure 1 The Catharanthus roseus plants used in this paper The condensation of catharanthine and vindoline is an absolute requirement for the formation of vinblastine and , later , vincristine As vindoline is required to synthesise the cytotoxic constituents but does not exist in the roots of C roseus , but only in the green parts of the plant , no vincristine nor vinblastine can be found in the roots of this species In the plant , vindoline is a major constituent ( up to 0 5% ). Major alkaloids in the roots include ajmalicine , catharanthine , and serpentine Another source mentions ajmalicine and serpentine are essentially present in the roots , whereas catharanthine and vindoline accumulate in aerial parts The aerial parts contain 0 2 - 1% alkaloids [ 3 ] Roots to be used in pharmacy must contain at least 0 4% ajmalicine and serpentine Catharanthine ( Figure 2 ) from Catharanthus roseus has been proposed to be a pharmacological treatment for addiction without the adverse side effects associated with ibogaine It "slows DA reuptake and increases extracellular DA in the nucleus accumbens through partial inhibition of DATs" [ 4 , 5 ] and potentiates GABAARs [ 6 ] The root alkaloids from C roseus root seem to be potent AChE inhibitors and catharanthine exhibited nicotinic receptor antagonism [ 7 ]. It has antidepressant activity via SERT inhibition and modulating NE [ 8 ] 2 Figure 2 Catharanthine Ajmalicine has antihypertensive effects [ 9 ] Experimental : Root material was macerated in basified isopropanol ( aq ammonia ) and concentrated to a small sample TLC ( silica , 0 2mm , glass backed , I2 visualisation ) gave poor separation of the constituents with a mixed solvent of acetone : white spirits : 1 : 1 White spirits gave better results with a major constituent Rf = 0 42 and some lesser Rf bands [ 1 ] https :// doi org / 10 1016 / j jep 2021 114647 [ 2 ] https :// aiche onlinelibrary wiley com / doi / epdf / 10 1002 / btpr 557 [ 3 ] Catharanthus roseus ( PROSEA ) - PlantUse English ( plantnet - project org ) [ 4 ] https :// scholarsarchive byu edu / studentpub _ uht / 242 [ 5 ] https :// scholarsarchive byu edu / etd / 9656 [ 6 ] https :// doi org / 10 1016 / j bcp 2022 114993 [ 7 ] https :// doi org / 10 1016 / j phymed 2009 10 008 [ 8 ] https :// doi org / 10 1016 / j ejphar 2022 175454 [ 9 ] https :// en wikipedia org / wiki / Ajmalicine Coronaridine has anti-addictive activity [3] as well as activity on the autonomic and central 3 nervous systems acting as a painkiller and respiratory depressant and is a potent AChE inhibitor Voacangine exhibited a slight central nervous stimulant effect and similar anti-addictive properties to ibogaine itself. Both ibogaine and V. africana extract may produce their central effects by altering dopaminergic and glutamatergic processes [4] Voacangine exhibited potent AChE inhibitory properties similar to the galantamine. Major alkaloids reported from Voacanga africana stem-bark include: voacamine (7.2%), voacangine (5.6%), voacristine (4.0%), voacorine (3.7%) etc. The bisindole alkaloids act as AChE and butyrylcholinesterase inhibitors and voacamine, 3,6-oxidovoacangine, and 5-hydroxy-3,6-oxidovoacangine from V. africana root bark exhibited significant cannabinoid CB1 receptor antagonism Ibogamine is apparently a powerful stimulant of the central nervous system, ibogamine and ibogaine presented a similar effect. Dos Santos & al. (2017) described the anti-addictive action of these alkaloids Vincamine is present in V. minor, V. major, and V. major var. variegata, while V. minor had the richest alkaloid content, although vincamine was without an effect on addiction it has nootropic and beneficial CNS activities. Five indole alkaloids including vincaminorine, vincaminoreine, minovine, minovincine, and vincamine were isolated from the aerial parts of V. minor. Vincamine was found to be the dominant alkaloid in this plant with the content of 0.057% of the dried plant mass. "V. minor contains monomeric eburnamine-type indole alkaloids including vincamine which has modulatory effects on brain circulation and neuronal homeostasis as well as antihypoxic and neuroprotective potencies. Vincamine is used for the prevention and treatment of cerebrovascular insufficiencies and disorders. A large body of clinical evidence indicates a favorable effect of vincamine in a number of brain disorders of elderly patients, such as memory disturbances, vertigo, transient ischemic deficits, and headache. It increases cerebral blood flow, oxygen consumption and glucose utilisation. In general, Vinca minor is known to be a valuable medicinal plant." 4 Source: http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3813059/ Flowers of Tabernaemontana divaricata contain voacangine, catharanthine and O-acetyl vallesamine and have potent pain-relieving effects through opioidergic mechanisms. The plant is used in traditional medicine as an anti-epileptic, anti-manic, brain tonic, and anti- oxidant with uses as a rejuvenating and neuro-tonic remedy to help forgetfulness and improve memory. It had potent anti-acetylcholinesterase activity and crude extracts demonstrated CNS depressant activity Alstonine is a potential innovative antipsychotic. It is used traditionally as a plant medicine named ‘uhuma obi-nwok’, in Igbo ‘the heart of man’. The plant is used to treat different types of ‘madness’, epilepsy, and is in general considered to be a sedative. To treat severe ‘madness’ the ground root is boiled in water (a piece of root about 10 cm long and 5 cm in diameter is prepared in 250 ml of water) until the liquid turns into a reddish-brown in color; the initial loading dose for an adult is one cup. Alstonine not only increases social interaction in normal mice, but also averts social deficits attributable to negative symptoms of schizophrenia. 5 Alstonine Alstonine not only increases social interaction in normal mice, but also averts social deficits attributable to negative symptoms of schizophrenia. It has potential as a drug for the management of negative symptoms in schizophrenia. The behavioural profile of alstonine appears to be closer to that of newer rather than older antipsychotics, it nevertheless differs from clozapine in its ability to reverse MK801-induced hyperlocomotion and social deficit, and by lacking epileptogenic properties. An unusual mechanism of action for alstonine is also here suggested by its effects on levels of DA in frontal cortex and striatum. Lack of changes in HVA levels suggests unchanged DA metabolism at the synaptic level, whereas increases in DOPAC levels suggests augmented intraneuronal catabolism. Alstonine induced increases in 5HT levels in frontal cortex, and of 5HIAA in frontal cortex and striatum. The suggestion is that alstonine acts as a inverse agonist at 5- HT2A/Cs [1] https://pubs.acs.org/doi/pdf/10.1021/acsmedchemlett.2c00214 [2] https://scholarsarchive.byu.edu/etd/9656/ [3] https://doi.org/10.1016/0006-8993(94)90948-2 [4] https://doi.org/10.3109/13880209.2012.658478 6