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Molecules (Basel, Switzerland) Oct 2019The reaction of papaverine with a series of Baran Diversinates is reported. Although the yields were low, it was possible to synthesize a small biodiscovery library...
The reaction of papaverine with a series of Baran Diversinates is reported. Although the yields were low, it was possible to synthesize a small biodiscovery library using this plant alkaloid as a scaffold for late-stage C-H functionalization. Ten papaverine analogues (-), including seven new compounds, were synthesized. An unexpected radical-induced exchange reaction is reported where the dimethoxybenzyl group of papaverine was replaced by an alkyl group. This side reaction enabled the synthesis of additional novel fragments based on the isoquinoline scaffold, which is present in numerous natural products. Possible reasons for the poor yields in the Diversinate reactions with this particular scaffold are discussed.
Topics: Carbon-13 Magnetic Resonance Spectroscopy; Electrons; Models, Molecular; Papaverine; Proton Magnetic Resonance Spectroscopy; Sulfinic Acids
PubMed: 31683610
DOI: 10.3390/molecules24213938 -
Angiology Nov 1977
Review
Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Drug Evaluation; Drug Evaluation, Preclinical; Humans; Papaverine; Procainamide; Quinidine; Structure-Activity Relationship; Verapamil
PubMed: 333993
DOI: 10.1177/000331977702801102 -
Drug Development Research Sep 2022The causative agent of coronavirus disease-2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the host cells via an...
The causative agent of coronavirus disease-2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), enters the host cells via an angiotensin-converting enzyme 2 (ACE2)-mediated endocytosis-dependent manner. Because ACE2 is highly expressed in the heart, SARS-CoV-2 can severely infect heart tissue and arteries, causing acute and chronic damage to the cardiovascular system. Therefore, special attention should be paid to finding appropriate agents to protect this vital system during COVID-19 treatment. Papaverine is a unique vasodilator alkaloid that is clinically used in the treatment of vasospasm. Interestingly, this compound has potent and direct effects on a wide range of viruses, and could also prevent viral exploitation mechanisms of the host cell facilities by inhibiting some cellular signaling pathways such as p38 MAPK. This pathway was recently introduced as a promising target for the treatment of COVID-19. Papaverine also has anti-inflammatory effects which is useful in combating the hyper-inflammatory phase of the COVID-19. Unlike some medications that have severe dosage-restrictions in the treatment of COVID-19 due to cardiac side effects, papaverine is recommended for use in many heart disorders. The ability of papaverine to treat COVID-19 has become more promising when the results of some extensive screenings showed the strong ability of this compound to inhibit the cytopathic effects of SARS-CoV-2 with EC of 1.1 μM. Having several therapeutic effects along with desired safety profile raises this hypothesis that papaverine could be a promising compound for the suppression of SARS-CoV-2 and prevention of ischemia/vasoconstriction-related complications in COVID-19 disease, especially in patients with underlying cardiovascular diseases (CVDs).
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Cardiovascular Diseases; Humans; Papaverine; Peptidyl-Dipeptidase A; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35706384
DOI: 10.1002/ddr.21961 -
Paediatric Anaesthesia Jun 2022Maintaining the patency of peripheral arterial lines in pediatric patients during surgery can be challenging due to multiple factors, and catheter-related arterial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Maintaining the patency of peripheral arterial lines in pediatric patients during surgery can be challenging due to multiple factors, and catheter-related arterial vasospasm is a potentially modifiable cause. Papaverine, a potent vasodilator, improves arterial line patency when used as a continuous infusion in the pediatric intensive care setting, but this method is not convenient during surgery.
AIM
Extrapolating from the benefit seen in the intensive care unit, the authors hypothesize that a small-volume intraarterial bolus of papaverine immediately after arterial line placement will reduce vasospasm-related arterial line malfunction.
METHODS
This was a prospective, randomized, double-blind study. Patients less than 17 years of age undergoing cardiac surgery were enrolled. Patients were randomized into the heparin or papaverine groups. Immediately after arterial line insertion, an intraarterial bolus of heparin (2 units/ml, 1 ml) or papaverine (0.12 mg/ml, 1 ml) was administered (T1, Figure 1). An optimal waveform was defined as the ease of aspirating a standardized blood sample within 30 s, absence of cavitation when sampling, absence of color change at the catheter site during injection, and presence of a dicrotic notch. The primary outcome evaluated was the presence of an optimal arterial waveform at 5 min after the first randomized dose (T1 + 5 min). The secondary outcomes were the presence of optimal arterial waveform an hour after the first dose and the ability of papaverine to rescue suboptimal waveforms.
RESULTS
A total of 100 patients were enrolled in the study. Twelve patients were excluded from the analysis. Complete datasets after randomization were available in 88 patients (heparin group, n = 46; papaverine group, n = 42). At baseline, groups were similar for age, weight, arterial vessel size, and arterial line patency. At T1 + 5 min, an improvement in the waveform characteristics was observed in the papaverine group (heparin,39% [8/46] vs. papaverine, 64% [27/42]; p = .02; odds ratio, 2.8; 95% CI, 1.2 to 6.6, Figure 3, Table 2). At the end of 1 h, both groups showed continued improvement in arterial line patency. After the second dose, a higher number of patients in the heparin group had suboptimal waveforms and were treated with papaverine (heparin,37% [17/46] vs. papaverine,17% [7/42], p = .05). Patients in the heparin group treated with papaverine showed significant improvement in patency (13/17 vs. 3/7, p = .01). No serious adverse events were reported.
CONCLUSIONS
In pediatric patients, papaverine injection immediately after peripheral arterial catheter placement was associated with relief of vasospasm and improved initial arterial line patency. Further, papaverine can be used as a rescue to improve and maintain arterial line patency.
Topics: Cardiac Surgical Procedures; Catheters; Child; Double-Blind Method; Heparin; Humans; Papaverine; Prospective Studies
PubMed: 35304932
DOI: 10.1111/pan.14442 -
Angewandte Chemie (International Ed. in... Nov 1976
Topics: Ethers, Cyclic; Papaverine
PubMed: 826193
DOI: 10.1002/anie.197606851 -
Urologia Internationalis 1988The introduction in 1982 of vasoactive agents for intracavernous injection represents a milestone in the diagnosis and treatment of erectile dysfunction. Two... (Review)
Review
The introduction in 1982 of vasoactive agents for intracavernous injection represents a milestone in the diagnosis and treatment of erectile dysfunction. Two preparations, the single drug papaverine hydrochloride and the combination of phentolamine mesylate and papaverine hydrochloride, hold great promise. In the last few years, the use of vasoactive drugs for evaluation and treatment of erectile dysfunction has become accepted worldwide. This paper explores the diagnostic and therapeutic possibilities and hazards implied in the method, assessing the advantages and drawbacks of papaverine and the combination product.
Topics: Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Papaverine; Penile Erection; Phentolamine
PubMed: 3291360
DOI: 10.1159/000281308 -
Journal of the American Pharmaceutical... May 1977
Topics: Biological Availability; Delayed-Action Preparations; Drug Industry; Humans; Papaverine
PubMed: 874257
DOI: 10.1016/s0003-0465(16)34191-x -
Journal of the American Academy of... Nov 1985Papaverine hydrochloride taken by mouth in doses of 100 mg four to six times daily or in 150-mg timed-release capsules two or three times daily is often effective in...
Papaverine hydrochloride taken by mouth in doses of 100 mg four to six times daily or in 150-mg timed-release capsules two or three times daily is often effective in significantly decreasing itching in patients with atopic dermatitis. When used orally, as described here, it does not appear to have beneficial effects in other itchy dermatoses. It should be used as adjuvant treatment in combination with other accepted forms of therapy, since it alone cannot reverse the chronic skin changes brought about by months or years of scratching and rubbing.
Topics: Adrenal Cortex Hormones; Dermatitis, Atopic; Humans; Papaverine; Phosphodiesterase Inhibitors
PubMed: 4078076
DOI: 10.1016/s0190-9622(85)70227-7 -
The New England Journal of Medicine Jan 1970
Topics: Humans; Liver; Papaverine
PubMed: 5409818
DOI: 10.1056/NEJM197001222820418 -
Joint Diseases and Related Surgery Apr 2024The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat...
OBJECTIVES
The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat model.
MATERIALS AND METHODS
Forty-eight adult male Sprague-Dawley rats (range, 300 to 400 g) were used in this study conducted between October and November 2022. The rats were divided into three groups, with each group further subdivided into two for sacrifice on either the 15 (early period) or 30 (late period) day after surgery. The first (control) group received no treatment following Achilles tendon repair, while papaverine was intraperitoneally administered every other day for 10 days in the second group and locally in the third group after surgery. On the 15 and 30 days, the rats were sacrificed, and their Achilles tendons were subjected to biomechanical testing and histopathological evaluation.
RESULTS
Histopathologically, there were no significant differences among the groups on the 15 day. However, on the 30 day, the locally applied papaverine group exhibited superior histopathological outcomes compared to the control group (p<0.05). Concerning the highest tensile strength values before rupture, the biomechanical assessment showed that the group receiving local papaverine treatment in the early period and both the group with systemic papaverine treatment and the one with local papaverine treatment in the late period displayed a statistically significant advantage compared to the control group (p<0.05).
CONCLUSION
Locally administered papaverine has positive biomechanical effects in the early period and exhibits a positive correlation both histopathologically and biomechanically in the late period. Novel therapeutic options may be provided for patients through these findings.
Topics: Animals; Achilles Tendon; Papaverine; Rats, Sprague-Dawley; Male; Tissue Adhesions; Wound Healing; Tendon Injuries; Rats; Tensile Strength; Injections, Intraperitoneal; Biomechanical Phenomena; Disease Models, Animal
PubMed: 38727117
DOI: 10.52312/jdrs.2024.1656