Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application

Abstract

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.

The effect of papaverine on tendon healing and adhesion in rats following Achilles tendon repair

“…Although the in vivo effects of papaverine have not been fully elucidated, it is known to increase cAMP (cyclic adenosine monophosphate) and cGMP (cyclic guanosine monophosphate) levels through the inhibition of phosphodiesterase enzymes. [ 23 ] These intracellular secondary messengers play pivotal roles in transmitting various physiological stimuli and regulating numerous physiological processes, including vascular resistance, cardiac output, visceral motility, immune responses, inflammation, neuroplasticity, vision, and reproduction. [ 24 , 25 ]…”

“…Papaverine is also widely used in urology for diagnosing and treating impotence. [ 23 ] Interestingly, a study evaluating the effects of sildenafil, another phosphodiesterase inhibitor used in impotence treatment, on Achilles tendon healing reported positive histopathological effects. [ 32 ] In our study, while biomechanical effects were evident in the late period, positive differences were observed in all groups receiving papaverine treatment.…”

Monofloral Corn Poppy Bee-Collected Pollen—A Detailed Insight into Its Phytochemical Composition and Antioxidant Properties

“…In particular, the alkaloids detected in PBP extracts can actually exert beneficial effects for humans through consumption. For instance, isoquinoline alkaloids possess anticancer properties [50], while papaverine, per se, has been recognized as a miracle compound with different health benefits [51]. It has been demonstrated that local application of papaverine on patients with end-stage renal disease can induce a reduction in arteriovenous fistula maturation without any additional difficulties [52].…”