Protopine has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an analgesic. It is one of the compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Protopine can selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Classical antihistaminics antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. Protopine can also function as platelet aggregation inhibitors which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Protopine inhibits the contractility of isolated cardiac papillary muscles and the proliferation of vascular smooth muscle cells induced by endothelin. It also shortens action potential duration and prolongs the effective refractory period in guinea pig cardiac papillary muscles. The protective effect on rat heart from ischemia_reperfusion damage and the relaxation of rat thoracic aorta induced by protopine have been related to the inhibition of Ca2+ influx through both voltage- and receptor-operated Ca2+ channels. Protopine has been the focus of a large number of biological studies in which they both exhibited, for instance, anti-parasitic activity and only weak cytotoxicity in comparison with other types of isoquinoline alkaloids. Protopine was found to be cytoprotective against oxidative stress induced cell death in vitro. The alkaloid was shown to have anti-arrhythmic, anti-thrombotic, anti-inflammatory, and hepatoprotective effects in animal models. The biological activity of protopine may be associated with its ability to inhibit calcium, sodium, and potassium channels. (PMID:15588728; PMID:21419197; L2104)