Alstonine is an
indoloquinolizidine alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
and putative
antipsychotic
Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...
constituent of various plant species including ''
Alstonia boonei
''Alstonia boonei'' is a very large, deciduous, tropical-forest tree belonging to the family Apocynaceae. It is native to tropical West Africa, with a range extending into Ethiopia and Tanzania. Its common name in the English timber trade is che ...
'', ''
Catharanthus roseus
''Catharanthus roseus'', commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a species of flowering plant in the family Apocynaceae. It is native and endemic to M ...
'', ''
Picralima nitida
''Picralima'' is a plant genus in the family Apocynaceae, first described as a genus in 1896. It contains only one known species, ''Picralima nitida'', native to tropical Africa (Benin, Ghana, Ivory Coast, Nigeria, Gabon, Cameroon, Cabinda, Cent ...
'', ''
Rauwolfia caffra'' and ''
Rauwolfia vomitoria''.
In preclinical studies alstonine attenuates
MK-801
Dizocilpine ( INN), also known as MK-801, is a pore blocker of the ''N''-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is ...
-induced hyperlocomotion, working memory deficit and social withdrawal. It also possesses
anxiolytic
An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...
-like effects in preclinical studies,
[ attenuates amphetamine-induced lethality and stereotypy as well as ]apomorphine
Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non- selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antag ...
-induced stereotypy,[ and attenuates ]haloperidol
Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...
-induced catalepsy
Catalepsy (from Ancient Greek , , "seizing, grasping") is a nervous condition characterized by muscular rigidity and fixity of posture regardless of external stimuli, as well as decreased sensitivity to pain.
Signs and symptoms
Symptoms in ...
. These effects appear to be mediated by stimulation of the 5-HT2C receptor. In addition, alstonine, similarly to clozapine
Clozapine is a psychiatric medication and is the first atypical antipsychotic (also called second-generation antipsychotic). It is primarily used to treat people with schizophrenia and schizoaffective disorders who have had an inadequate respo ...
, indirectly inhibits the reuptake
Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the Synapse, pre-synaptic neuron at a synapse) or glial cell after it has performed its function of ...
of glutamate in hippocampal
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, an ...
slices. Unlike clozapine however, the effect of which is abolished by the D2 receptor agonist apomorphine, alstonine requires 5-HT2A and 5-HT2C receptors to produce this effect, as it is abolished by antagonists of these receptors. Also unlike clozapine, alstonine lacks pro-convulsant activity in mice.
See also
* Ajmalicine
Ajmalicine, also known as δ-yohimbine or raubasine, is an antihypertensive drug used in the treatment of high blood pressure. It has been marketed under numerous brand names including Card-Lamuran, Circolene, Cristanyl, Duxil, Duxor, Hydroxysarp ...
* Corynanthine
Corynanthine, also known as rauhimbine, is an alkaloid found in the ''Rauvolfia'' and ''Corynanthe'' (including ''Pausinystalia'') genera of plants. It is one of the two diastereoisomers of yohimbine, the other being rauwolscine. It is also rel ...
* Deserpidine
Deserpidine ( INN) or reserpidine (USAN) is an antihypertensive drug related to reserpine which occurs naturally in ''Rauvolfia
''Rauvolfia'' (sometimes spelled ''Rauwolfia'') is a genus of evergreen trees and shrubs, commonly known as de ...
* Mitragynine
* Rauwolscine
Rauwolscine, also known as isoyohimbine, α-yohimbine, and corynanthidine, is an alkaloid found in various species within the genera ''Rauvolfia'' and ''Corynanthe'' (including ''Pausinystalia''). It is a stereoisomer of yohimbine. Rauwolscine is ...
* Spegatrine
Spegatrine is an α1- and α2-adrenergic receptor antagonist isolated from '' Rauvolfia verticillata''. Its dimer dispegatrine has greater antagonist affinity for α-adrenergic receptors.
See also
* Ajmalicine
* Corynanthine
* Rauwolscine
...
* Reserpine
Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces m ...
* Rescinnamine
* Yohimbine
Yohimbine (), also known as quebrachine, is an indole alkaloid derived from the bark of the African tree '' Pausinystalia johimbe''; also from the bark of the unrelated South American tree ''Aspidosperma quebracho-blanco''. Yohimbine is an α2 ...
References
Indoloquinolizines
Antipsychotics
Indole alkaloids
Serotonin receptor agonists
Methyl esters
Heterocyclic compounds with 5 rings
Quaternary ammonium compounds
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