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Taking into account the increasing use of cyclodextrins (CDs) to overcome drawbacks of drugs like antihypertensive, complex formation with of CDs seems to be a good pharmaceutical strategy to improve stability, solubility, bioavailability and reduction of side effects, thus facilitating the control of hypertension. The main objective of this short communication is to demonstrate the antihypertensive potential of complexed compounds with β-cyclodextrins and their clinical applications. This short communication identified and illustrated that β-cyclodextrin-based systems are promising sources that provide improved pharmacokinetic and formulation conditions, and important applications have been established by many research groups, optimizing β-CDs derivative systems for oral drug therapy, especially in hypertension.

Introduction: Decreased bioavailability of nitric oxide (NO) plays a mechanistic role in hypertension and myocardial infarction. NO donors are potent vasodilators, but often exhibit toxicity or vascular tolerance. The aim of this study was to investigate the vascular activity possible tachyphylaxis of NONO2P, a novel NO donor. Methods: Male Wistar rats were euthanized, and the superior mesenteric artery was isolated for recordings of isometric force, and in vivo experiments were performed to evaluate blood pressure in non-anesthetized normotensive rats. Results: Cumulative administration of the NONO2P (10 -13 to 3x10 -6 M) induced endothelium-independent relaxation (Emax:111.51 ± 2.31%; pD2: 8.51 ± 0.08, n=9) in arterial rings pre-contracted with phenylephrine (Phe,1μM). However, the relaxation was reduced in pre-contracted rings with Phe exposed to Tyrode's solution containing 20 mM of K + (E max : 102.83 ± 2.10%; pD2: 7.73 ± 0.04, n=6), suggesting the participation of K + channels in the relaxation. The presence of the specific soluble guanylyl cyclase (sGC) inhibitor, ODQ (10μM), abolished the vasorelaxant effect (E max : 15.38 ± 11.85%, n=7). Pre-incubation with cyclopiazonic acid (CPA) (10μM), inhibitor of sarcoendoplasmic reticulum calcium ATPase (SERCA), shifted the relaxation concentration-response to the right (E max : 106.17 ± 3.06%; pD2: 7.69 ± 0.04, n=6). Interestingly, repeated NONO2P administration did not induce tachyphylaxis, and NONO2P presented similar maximum efficacy to sodium nitroprusside (SNP) (E max : 114.24 ± 3.47%; pD2: 9.40 ± 0.04, n=6). Moreover, NONO2P lowered blood pressure in normotensive rats. Conclusion: The endothelium-independent vasorelaxant effect induced by NONO2P involves both sGC, SERCA and K + channel activation, and NONO2P does not appear to cause tachyphylaxis. NONO2P is able to promote vasorelaxation with the same magnitude as SNP. Finally, NONO2P reduces blood pressure, becoming a promising molecule as a novel therapeutic alternative for the treatment of cardiovascular diseases.

Erectile dysfunction (ED) is considered a public health problem with numerous risk factors, such as hypertension. Besides the existing oral treatment for ED, there are individuals that do not respond to or present numerous side effects to this therapy. Changes in the TRP channels can lead to several clinical complications, such as hypertension. More specifically, the cooling-sensing TRPM8 channel could be a novel target for the development of new drugs. In this line, menthol, a natural product TRPM8 channel agonist may be a molecule for use to treat erectile dysfunction. Then, we conducted a patent review to evaluate the application of menthol focusing on the treatment of erectile dysfunction. The search was conducted on Espacenet® associating A61K31/045 and A61K36/534 codes or using keywords, “erectile dysfunction AND menthol”. We analyzed 1,331 patents, which fourteen patents were found with the use of menthol in the genitourinary system. Although the patents had menthol in their formulations, none went directly to the development of pharmaceutical applications to treat erectile dysfunction. Taking these data into account, the use of menthol in the treatment of erectile dysfunction has been underexplored and is an opportunity for research and technological development based on a high innovation potential.

The past two years were deeply marked by the emergence of a global pandemic caused by the worldwide spread of the virus severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. The plethora of repercussions on the health of those affected is extensive, ranging from asymptomatic individuals, mild flu-like disease, and severe respiratory failure, eventually leading to death. Despite this predilection for the respiratory system, the virus is responsible for multisystemic manifestations and soon became clear that neurological involvement was a frequent issue of coronavirus disease 2019 (COVID-19). Much have been pointed out about the neurotropic nature of the virus, the ways by which it invades and targets specific structures of the central nervous system, and the physiopathology behind the neurologic manifestations associated with it (namely encephalomyelitis, Guillain-Barré syndrome, lacunar infarcts, and vascular dysfunction, just to list a few). This chapter aims to raise light about the association between COVID-19 and the mechanisms of acute symptomatic seizures, through neurotropism and neuroinvasion features of SARS-CoV-2, and to review the variety of clinical presentations reported so far.