Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application

The pharmacological actions of benzylisoquinoline alkaloids are quite substantial, and have recently attracted much attention. One of the principle benzylisoquinoline alkaloids has been found in the unripe seed capsules of Papaver somniferum L. Although it lacks analgesic effects and is unrelated to the compounds in the morphine class, it is a peripheral vasodilator and has a direct effect on vessels. It is reported to inhibit the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) phosphodiesterase in smooth muscles, and it has been observed to increase intracellular levels of cAMP and cGMP. It induces coronary, cerebral, and pulmonary artery dilatation and helps to lower cerebral vascular resistance and enhance cerebral blood flow. Current pharmacological research has revealed that papaverine demonstrates a variety of biological activities, including activity against erectile dysfunction, postoperative vasospasms, and pulmonary vasoconstriction, as well as antiviral, cardioprotective, anti-inflammatory, anticancer, neuroprotective, and gestational actions. It was recently demonstrated that papaverine has the potential to control SARS-CoV-2 by preventing its cytopathic effect. These experiments were carried out both in vitro and in vivo and require an extensive understanding of the mechanisms of action. With its multiple mechanisms, papaverine can be considered as a natural compound that is used to develop therapeutic drugs. To validate its applications, additional research is required into its precise therapeutic mechanisms as well as its acute and chronic toxicities. Therefore, the goal of this review is to discuss the major studies and reported clinical studies looking into the pharmacological effects of papaverine and the mechanisms of action underneath these effects. Additionally, it is recommended to conduct further research via significant pharmacodynamic and pharmacokinetic studies.