Product Code Database
Aporphine is an alkaloid with the chemical formula . It is the core chemical substructure of the aporphine alkaloids, a subclass of quinoline alkaloids. It can exist in either of two forms, ( R)-aporphine and ( S)-aporphine.
In vitro, tests of some aporphine derivatives isolated from Cassytha filiformis, namely, actinodaphnine, cassythine, and dicentrine, showed antiparasitic activity against Trypanosoma brucei. Investigation of possible mechanisms revealed that the compounds bind to DNA and act as intercalating agents, in addition to inhibiting topoisomerase activity.
Aporphine natural products occur with either the (R)- or (S)- Isomer, or they can be Chirality. Furthermore, morphine-based natural products can be heated in acid to give aporphine degradation products; one example is the FDA-approved Parkinson's drug apomorphine, which was first discovered by the Finnish chemist Adolf Edvard Arppe in 1845.
Historically, apomorphine has seen a variety of clinical uses including as a treatment for anxiety and cravings in alcoholics, as an Vomiting, and more recently in treating erectile dysfunction. It was also used as a private treatment for heroin addiction. Still, there is no clinical evidence that apomorphine is an effective and safe treatment for opiate addiction.
Currently, apomorphine is used in the treatment of Parkinson's disease. It is a potent emetic, typically administered with an antiemetic such as domperidone. Apomorphine is also utilized in veterinary medicine to induce therapeutic emesis in canines that have recently ingested toxic or foreign substances.
Several natural products including semisynthetic analogs belonging to the aporphine class have been synthesized. These include apomorphine by Neumeyer and Raminelli, Pukateine by Happel, Isocorydine by Di, Nuciferine and Oliveroline by Cuny, Glaucine by Meyers, Dicentrine by Cava, and Lysicamine by Raminelli.
Some aporphine alkaloids (such as crebanine) have been found to present Arrhythmia activity and higher toxicity. In one study, a couple of target derivatives were evaluated for their anti-arrhythmic potential in the mouse model of ventricular fibrillation. Here, preliminary structure-activity/toxicity relationship analyses were carried out. Of these target derivatives, a certain bromo-substituted product of crebanine displayed significant anti-arrhythmic activity and a lower toxicity. In a significant number of rats, this product caused reduction in the incidence of VF, increase in the resumption of sinus rhythm from arrhythmia, and increase in maintaining sinus rhythm. The results from this limited study indicate that this specific aporphine alkaloid could be considered as a promising candidate in the treatment of arrhythmia.
Aporphine alkaloids present in Litsea glutinosa, a tropical plant with antioxidant and anti-parasitic properties, are claimed to contribute to anti-cancer activity. Research has illustrated the antiproliferative and cytotoxic effects of aporphine-containing extracts of Litsea glutinosa.
( R)-Aporphine is a dopamine receptor D1 antagonist with a Ki of 717nM and a dopamine receptor D2 antagonist with a Ki of 527nM. Aporphine and its related alkaloids bulbocapnine, boldine, glaucine, and corytuberine are antipsychotic, exert naloxone-reversible Nociception activity and, except for corytuberine, are anticonvulsant. Some derivatives of aporphine such as ( S)-(+)- N-propylnorapomorphine have potential as low side effect profile antipsychotics. ( S)-(+)- N-Propylnorapomorphine is highly selective for meso-limbic dopaminergic tracts and function as efficacious partial agonists, with no elevation in prolactin.
In addition to Nymphaea Caerulea, the Sacred Lotus Nelumbo nucifera, a member of the Nelumbo species, contains aporphine alkaloids such as nuciferine.
In another study, investigations of whether systemic injection of apomorphine and its oxidation derivative 8-oxo-apomorphine-semiquinone (8-OASQ) could induce DNA damage in mice brain, using the single-cell gel assay. 8-OASQ induced DNA damage in the brains at 1 and 3 h, but not at 24 h after treatment whereas apomorphine induced a slight increase in brain DNA damage frequency at 3 h after treatment, suggesting that both drugs display genotoxic activity in brain tissue.
|
|
