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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.<\/jats:p>","DOI":"10.3390\/molecules28073149","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T02:10:13Z","timestamp":1680487813000},"page":"3149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Papaverine: A Miraculous Alkaloid from Opium and Its Multimedicinal Application"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0585-8500","authenticated-orcid":false,"given":"Sania","family":"Ashrafi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1831-2278","authenticated-orcid":false,"given":"Safaet","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh"},{"name":"Drugs and Toxins Research Division, BCSIR Laboratories Rajshahi, Bangladesh Council of Scientific and Industrial Research, Rajshahi 6206, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5855-8731","authenticated-orcid":false,"given":"Arifa","family":"Sultana","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3006-6206","authenticated-orcid":false,"given":"Asef","family":"Raj","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7567-4796","authenticated-orcid":false,"given":"Nazim Uddin","family":"Emon","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Science and Engineering, International Islamic University Chittagong, Chittagong 4318, Bangladesh"},{"name":"Department of Chemistry and Biochemistry, Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahmida Tasnim","family":"Richi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasnuva","family":"Sharmin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myunghan","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-3894","authenticated-orcid":false,"given":"Moon Nyeo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-156X","authenticated-orcid":false,"given":"Bonglee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1097\/ACO.0000000000000670","article-title":"Spinal Cord Perfusion Protection for Thoraco-Abdominal Aortic Aneurysm Surgery","volume":"32","author":"Arora","year":"2019","journal-title":"Curr. 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