Calcium Ion Antagonist Research Articles

In vitro ischemic preconditioning mediates the Ca2+/CaN/NFAT pathway to protect against oxygen-glucose deprivation-induced cellular damage and inflammatory responses

Oxygen-glucose deprivation (OGD) is a critical model for studying hypoxic-ischemic cerebrovascular disease in vitro. This paper is to investigate the protection of OGD-induced cellular damage and inflammatory responses by OGD preconditioning in vitro, to provide a theoretical basis for OGD preconditioning to improve the prevention and prognosis of ischemic stroke. OGD or OGD preconditioning model was established by culturing the PC12 cell line in vitro, followed by further adding A23187 (calcium ion carrier) or CsA (calcium ion antagonist). Cell viability was detected by MTT, apoptosis by Hoechst 33,258 staining, the levels of TNF-α and IL-1β mRNA by RT-qPCR and ELISA, and the levels of CaN, NFAT, COX-2 by RT-qPCR and Western blot. Cell viability was decreased, and apoptosis, inflammatory cytokines, and CaN, NFAT, and COX-2 levels were notably increased upon OGD, while OGD pretreatment significantly increased cell viability and decreased apoptosis, inflammation, and the Ca2+/CaN/NFAT pathway. Treatment with A23187 decreased cell viability, promoted apoptosis, and significantly increased TNF-α, IL-1β, CaN, NFAT, and COX-2 levels, while CsA treatment reduced the opposite results. In vitro OGD preconditioning mediates the Ca2+/CaN/NFAT pathway to protect against OGD-induced cellular damage and inflammatory responses.

Genetic and phenotypic frequency distribution of ACE, ADRB1, AGTR1, CYP2C9*3, CYP2D6*10, CYP3A5*3, NPPA and factors associated with hypertension in Chinese Han hypertensive patients.

We analyzed the polymorphisms of 7 antihypertensive drugs-related genes and the factors associated with hypertension in hypertensive patients of Han ethnicity in Qingyang, China. A total of 354 hypertensive patients of Han ethnicity were enrolled from Qingyang, China. The ACE (I/D), ADRB1 (1165G > C), AGTR1 (1166A > C), CYP2C9*3, CYP2D6*10, CYP3A5*3 and NPPA (T2238C) polymorphisms were assessed. Clinical data of patients was also obtained. The influencing factors of hypertension were evaluated. The genotype frequencies of ACE, ADRB1, AGTR1, CYP2C9, CYP3A5 and NPPA loci were in Hardy-Weinberg equilibrium, with mutation frequencies of 39.27%, 74.29%, 6.21%, 4.80%, 72.46% and 0.71%, respectively. CYP2D6 locus was not in Hardy-Weinberg equilibrium. There was no statistical difference in allele frequencies between different genders (P > .05). There was significant difference in the frequencies of ACE (I/D) and NPPA (T2238C) loci among different regions of China (P < .05). Gender, ACE (I/D) and ADRB1 (1165G > C) gene polymorphism, smoking, homocysteine and HDL levels were associated hypertension. The mutation frequencies of ADRB1 (1165G > C) and CYP3A5*3 were high in hypertensive patients of Han ethnicity in Qingyang, suggesting these patients may be more sensitive to beta-blockers and calcium ion antagonists. Meanwhile, hypertension was associated with gender, ACE (I/D) and ADRB1 (1165G > C) gene polymorphisms, smoking, homocysteine and HDL levels.

Hematological Profiles and Alkaline Phosphatase Enzyme of Tissues in Male Mice Treated with Nifedipine Medication

It is well recognized that certain types of medications for treatment of antihypertensive , known as Calciumchannel blockers (CCBs) and calcium ion antagonists are two types of calcium ion antagonists., only workby blocking the free passage of Ca+. Nifedipine, amlodipine, felodipine, diltiazem, and other medicationsare among them..Fifteen Adult male mice weighing 180-250 gm were randomly divided into three groupsand housed at the College of Science’s animal house, where they were fed a regular mice diet of water andpellets ad libitum.. Tthe control group (n=5) were treated with 1ml of distilled water, the 2nd group (n=5)were treated orally with 20 mg/kg body weight of Nifedipine while the 3rd group (n=5) were treated orallywith 60mg/kg by oral gavage for 35 days body weight of Nifedipine. The treatment was discontinued for 24hours before the animals were sacrificed..The data indicated biochemical parameters alkaline phosphatase (ALP) were found nonsignificantincreased in kidney and testicular tissues,but hematological parameters no any variance has been shownin both Hb,PCV,RBC, HCT, MCV, RDW and platelets in all test groups, whereas MCHC did show majorincreases in both dosage groups of nifedipine, but WBCs count data suggested a decrease in 20mg/Kgdosage only.We showed that nifedipine could reduce lymphocyte counts Substantial increases in monocyteand neutrophil counts were achieved at doses of 60 mg/kg BW when compared to the control group, andsignificant increases in monocyte and neutrophil counts were achieved at doses of 20 BW when comparedto the control group.,Above results indicate that the variations caused by nifedipine drug can have slightnegative effects on the parameters of kidney, testis enzymes and hematological parameters.

Efficacy of Edaravone in Combination with Dihydropyridine Calcium Ion Antagonist on Hypertensive Intracerebral Hemorrhage

This research article planned to investigate the efficacy of edaravone in combination with dihydropyridine calcium ion antagonist on hypertensive intracerebral hemorrhage. Between February 2017 and January 2019, we collected the clinical data from 126 hypertensive intracerebral hemorrhage patients and divided them into the control group and observation group, with 63 patients in each group. Patients in two groups all underwent the regular treatment, while those in the observation group took edaravone in combination with dihydropyridine calcium ion antagonist (nimodipine) for treatment. Following the treatment, we compared the clinical efficacy, plasmin endothelin 1, volume of edema and hematoma and National Institute of Health stroke scale scores. In the control group, the total effectiveness rate of treatment was 71.44 %, significantly lower than that of the observation group (p<0.05); following treatment, the level of endothelin 1 in plasma and the volumes of edema and hematoma were all decreased as compared to those before treatment and the decrease in the observation group was more evident (p<0.01). Before treatment, difference in the National Institute of Health stroke scale scores between the control group and the observation group was not evident (p>0.05), while after 2 and 4 w of treatment, patients in the observation group had scores of (12.43±4.07) and (7.52±1.84) points, significantly higher than those in the control group (p<0.01). Combined medication of edaravone and dihydropyridine calcium ion antagonist can benefit the patients with promising efficacy and improvement in nervous function.

Absorption, tissue disposition, and excretion of fasudil hydrochloride, a RHO kinase inhibitor, in rats and dogs.

Fasudil hydrochloride as an intracellular calcium ion antagonist that dilates blood vessels has exhibited a very potent pharmacological effect in the treatment of angina pectoris. The purpose of this study was to determine the absorption, distribution, and excretion profiles of fasudil in rats and beagle dogs, respectively, to clarify its pharmacokinetic pattern. A sensitive and reliable LC-MS/MS method has been developed and established and successfully applied to pharmacokinetic study, including absorption, tissue distribution, and excretion. The results revealed that in the range of 2-6 mg/kg, the pharmacokinetic behavior for instance, AUC and Cmax , in rats was observed in a dose dependent manner. However, the plasma concentrations were indicative of a significant gender difference in the pharmacokinetics of fasudil in rats, in terms of absolute bioavailability and excretion. Interestingly, the resulting data obtained from beagle dogs showed that there was no gender difference in the absolute bioavailability of fasudil hydrochloride after single or repeated administrations. In conclusion, this study characterized the pharmacokinetic pattern fasudil both in rats and beagle dogs through absorption, tissue distribution and excretion study. The findings may be valuable and provide a rationale for further study and its safe use in clinical practice.

Research development on modern pharmacological effect of tetrandrine

Han stephania, also known as Stephania tetrandra, expelling wind, relieve pain and inducing diuresis for removing edema, is a traditional Chinese medicine for treating rheumatic arthralgia. Alkaloids have an important pharmacodynamic basis in S. tetrandra, and tetrandrine is one kind content of bisbenzylisoquinoline alkaloids, which has many biological activities. These activities include anti-tumor in many ways, clinically inhibiting multiple inflammatory factors, preventing and treating liver fibrosis and renal fibrosis and many other kinds of fibrotic diseases, and in addition, tetrandrine could work synergistically with other drugs. In recent years, through in-depth research by scholars at home and abroad, it has been found that tetrandrine has a protective effect on the nervous system and ischemia-reperfusion injury. At the same time, as a calcium ion antagonist, tetrandrine could effectively block the deposition of calcium ions inside and outside the cell. In summary, the application prospect of tetrandrine in clinical practice is very extensive. In this paper, the pharmacological effects of tetrandrine and the possible mechanisms for these effects are summarized, and review its current research progress. It is hoped that the possible application direction of tetrandrine can be revealed more comprehensively, and provide better enlightenment and ideas for clinical application.

On the dimorphism and the pressure–temperature state diagram of racemic m-nisoldipine, a dihydropyridine calcium ion antagonist

The pressure-temperature phase diagram of the dimorphism of racemic m-nisoldipine is constructed using temperatures and enthalpies of fusion of forms A and B. At ordinary pressure, the transition from form B to form A is found to occur around 192K, which indicates that these polymorphs are enantiotropically related and that form A is stable at room temperature. Nevertheless, the phase relationship turns to be monotropic when pressures become greater than about 100MPa, which indicates that form B becomes the sole stable phase.

Comparison of the physical and thermodynamic stability of amorphous azelnidipine and its coamorphous phase with piperazine.

A major challenge in drug development is that the majority of drugs are water insoluble, and a powerful method to conquer this obstacle is to transfer a crystalline drug into its amorphous phase (AP) or coamorphous phase (CAP) with a coformer. In the present study, the physical and chemical stabilities of an AP and a CAP based on the dihydropyridine calcium ion antagonist azelnidipine (AZE) were investigated using thermal analysis and a solution chemistry method. The identification of two APs (named α-AP and β-AP, from crystalline α-AZE and β-AZE, respectively) and one AZE-piperazine CAP was attempted using powder X-ray diffraction, temperature modulated differential scanning calorimetry and Fourier-transform infrared spectroscopy. The transition thermodynamics from the two APs and the CAP to stable crystalline β-AZE (β-Cry) were investigated using a solubility method. The solubility of the two APs, the CAP and β-Cry in 0.01 M HCl medium at 298, 304, 310, 316 and 322 K was investigated; the values obtained were used to calculate the thermodynamic parameters of the transition reaction. The transition temperatures of α-AP, β-AP and the CAP to form β-Cry in 0.01 M HCl were 237.7, 400.3, and 231.4 K, respectively. The glass transition temperature (Tg) values of α-AP, β-AP and the CAP were 365.5, 358.9 and 347.6 K, respectively, indicating a high physical stability for α-AP. However, β-AP proved to be the most thermodynamically stable form at room temperature compared with α-AP and CAP in the 0.01 M HCl medium. As evidenced by those observations, no general relationship occurred between the solid physical stability and the solution chemical stability for AP and CAP. The kinetics of the solid-state decomposition, studied using DSC analysis, showed that the activation energies for decomposition of α-AP, β-AP and CAP at high temperatures were 133.0, 114.2 and 131.6 kJ mol−1, respectively.

Investigating the in vitro stereoselective metabolism of m-nisoldipine enantiomers: characterization of metabolites and cytochrome P450 isoforms involved.

m-Nisoldipine, as a novel 1,4-dihydropyridine calcium ion antagonist, was presented as a couple of enantiomers [(-), (+)-m-nisoldipine]. In this report, the in vitro metabolism of m-nisoldipine enantiomers was investigated in rat liver microsomes (RLM) by the combination of two liquid chromatography mass spectrometric techniques for the first time. The metabolites were separated and assayed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and further identified by comparison of their mass and chromatographic behaviors with reference substances. A total of 18 metabolites of (-)-m-nisoldipine and 16 metabolites of (+)-m-nisoldipine were detected, respectively, which demonstrated that (+)-m-nisoldipine is more metabolically stable than (-)-m-nisoldipine. In addition, the identified metabolic pathways of m-nisoldipine enantiomers were involved in dehydrogenation, oxidation and ester hydrolysis. Afterwards, based on high-performance liquid chromatography coupled to triple quadrupole linear ion trap mass spectrometry, various selective cytochrome P450 (CYP) enzyme inhibitors were employed to evaluate CYP isoforms. The results indicated that the inhibitors of CYP1A1/2, CYP2B1/2, 2D and 2C11 had no obvious inhibitory effects, yet the inhibitor of CYP 3A had a significant inhibitory effect on metabolism of m-nisoldipine enantiomers. This showed that CYP 3A might primarily metabolize m-nisoldipine in RLM.

Profil Disolusi Tablet Amlodipin dan Perbandingan Kadar Dua Produk Generik dengan Produk Inovator

Amlodipine is an antihypertensive and antianginal drug belonging to the class of dihydropyridine calcium antagonist (calcium ion antagonist). Amlodipine patent term expired in 2007, thus nowadays some national pharmaceutical manufacturers produce amlodipine as generics and branded generics medicine. In order to determine the quality of generic amlodipine, dissolution profile and contents of two generic amlodipine were studied by comparing them with their innovator product. The dissolution test was carried out using a type 2 (paddle) and the dissolved content was determined by using UV spectrophotometer, whereas amlodipine content tablet was determined by using HPLC (High Performance Liquid Chromatography). The results showed that all of the three tablets met the FDA requirements of dissolution, i.e.within 30 minutes they should be dissolved not less than 85%. All of the three tablets had the same dissolution profile p=0,521 (CI=95%), whereas both the generic and branded generic tablet compared to the innovator product had similar or comparables profile , (f2>50). The content of all three tablets are not significantly different with p=0,08 (CI = 95%). The highest content of amlodipine was found in amlodipine a tablet with an average content of 102,69%.

Structures and characterization of m-nisoldipine polymorphs

m-Nisoldipine, a dihydropyridine calcium ion antagonist, first synthesized in the School of Pharmaceutical Sciences, Hebei Medical University, exhibits two polymorphs A and B with different colors and morphologies. The single-crystal X-ray structure analysis reveals that polymorph A crystallizes in a monoclinic P21/c space group with a = 9.3045(2) A, b = 16.5991(5) A, c = 13.0018(3) A, β = 91.539(2)° and Z = 4, while B crystallizes in a triclinic space group of P with a = 7.4965(2) A, b = 11.4692(4) A, c = 12.3648(5) A, α = 68.093(2)°, β = 88.655(2)°, γ = 81.853(2)° and Z = 2. The m-nisoldipine molecules are connected through N–H⋯O hydrogen bonds between the carbonyl group and the amine group to form either a wavy chain for A or a linear chain for B. The two polymorphs show distinct physicochemical properties as characterized by IR, Raman, DSC and terahertz pulse spectroscopy. DFT theoretical calculations are also used to simulate the terahertz spectroscopy of the two polymorphs.

Solid State Characterizations and Analysis of Stability in Azelnidipine Polymorphs

Azelnidipine, a new dihydropyridine calcium ion antagonist, was protected by patent in Japan. In present study, identifications of the crystal phases, including two polymorphic and a pseudopolymorphic crystal forms of azelnidipine, were attempted using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), IR-, Raman-, THz-, and ss-NMR-spectroscopy. PXRD identified three different crystal forms, while, spectroscopy analysis provided the information of crystal structure involving intermolecular interactions. The transition thermodynamics of the azelnidipine polymorphs were extensively investigated by solubility method. The solubility of the two polymorphs of α and β in 50% ethanol at 25, 31, 37, 42, and 49°C was investigated; the values obtained were used to calculate the thermodynamic parameters of the transition reaction. The temperature of polymorphic phase transition in 50% ethanol was 50.78°C, and the values of ΔG(α,β)(θ), ΔH(α,β)(θ), and ΔS(α,β)(θ) at 25°C were -1.18 kJ·mol(-1), -14.81 kJ·mol(-1), and -45.73 J·mol(-1)·K(-1), respectively. Form β was proved to be thermodynamic stable form at room temperature and enantiotropically related with form α. The kinetics of the solid-state decomposition, studied using DSC analysis, showed that the activation energies of decomposition of the polymorphs α and β at high temperatures were 148.67 and 151.93 kJ·mol(-1).

In Vitro Dissolution Kinetics of Amlodipine Tablets Marketed in Russia Under Biowaiver Conditions

The current paper is devoted to in vitro dissolution kinetics studies of amlodipine tablets marketed in Russia under biowaiver conditions. Dissolution kinetics studies were carried out according to WHO Guidance. Dissolution profiles of test and reference (innovator) amlodipine tablets were considered equivalent. INTRODUCTION Over the past three decades, dissolution testing has evolved into a powerful tool for characterizing the quality of oral pharmaceutical products. For some solid dosage forms containing active pharmaceutical ingredients with special properties, a comparative in vitro dissolution profile similarity can be used to establish equivalence of test with reference product. Such studies, used to approve equivalence other than through in vivo equivalence testing, are called “biowaiver” (1). Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. It is indicated for the treatment of hypertension, chronic stable angina, and confirmed or suspected vasospastic angina (2). The chemical name of amlodipine is 3-ethyl 5-methyl 2-[(2aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4dihydropyridine-3,5-dicarboxylate. Its structure is shown in Figure 1. Solubility Amlodipine is described as slightly soluble in water in different Pharmacopoeias (3, 4). The experimental water solubility for amlodipine is 75.3 mg/L (5). The lowest solubility in the pH range from 1 to 6.8 at 37 °C is 1 mg/mL (1). Within the gastrointestinal pH range, amlodipine is an ionized compound (weak base) (5). The pKa of amlodipine is about 8.6 at 25 °C (5). Dosage form strength is expressed in mg of salt and is not equivalent to the free base. Amlodipine is listed in the WHO Model list of medicines as an antihypertensive medicine in a 5-mg tablet strength (6). Russia has Marketing Authorizations for amlodipine as an immediate-release dosage form in strengths of 2.5; 5, and 10 mg (7). Thus the D/S ratio for the amlodipine WHO Model List of Essential Medicines dose (5 mg) at a pH range of 1.2–6.8 is 5 mL and 10 mL for the highest dose marketed in Russia. Therefore, amlodipine is a “highly soluble” drug according to WHO Guidance (D/S ratio ≤ 250 mL). Permeability When an active pharmaceutical ingredient is absorbed to an extent of 85% or more, it is considered “highly permeable.” Amlodipine’s absolute bioavailability is 60–65%, but its permeability is classified as “high” due to metabolite excretion in urine (90–95%). Taking amlodipine solubility and permeability into account, according to WHO Guidances, amlodipine is assigned to BCS Class I (1). Thus, amlodipine in vitro equivalence may be evaluated under biowaiver conditions for BCS Class I (1). MATERIALS AND METHODS Chemicals Analytical grade concentrated hydrochloric acid, glacial acetic acid, potassium dihydrophosphate, disodium hydrophosphate dodecahydrate, and potassium chloride were used. e-mail: ramenskaia@mail.ru *Corresponding author. Figure 1. Structure of amlodipine. diss-17-03-04.indd 20 8/18/2010 1:42:43 PM dx.doi.org/10.14227/DT170310P20

Capillary electrophoretic enantioseparation of m‐nisoldipine using two different β‐cyclodextrins

The methods for the enantioseparation of m-nisoldipine, a new 1,4-dihydropyridine calcium ion antagonist, were developed. The elaborated methods of m-nisoldipine enantiomers separation were successfully performed using an anionic CD-sulfobutyl ether-beta-CD (SBE-beta-CD) or carboxymethyl-beta-CD as chiral selector. However, the results indicated that SBE-beta-CD was a better chiral selector for enantioseparation of the neutral m-nisoldipine. Furthermore, comparing the two SBE-beta-CDs, the derivative with a higher degree of substitution (DS) of 7.0 induced better enantioresolution than the one with low DS (4.0). In addition, possible chiral recognition mechanisms of dihydropyridines were discussed.

Research status of the mechanism and treatment for acute pancreatitis complicated with hepatic injury

Acute pancreatitis (AP) is characterized by its sudden onset and rapid progression and is often complicated by liver injury. AP-induced liver injury may develop into hepatic failure and even result in death. Thus, it is of importance to protect liver function and block injury-related pathways. In the pathogenesis of liver injury in AP, inflammatory cytokines, nuclear factor-kappa B (NF-κB) and oxygen free radicals play important roles. The complexity of the mechanism underlying the development of liver injury exerts, to some extent, a contribution to the difficulties in the treatment of this disease. Currently, the drugs used to treat the disease include L-arginine (L-Arg), calcium ion antagonists, somatostatin and a variety of inflammatory mediator inhibitors. Additionally, some traditional Chinese medicines such as tripterygium, wilfordii, rhubarb and salvia miltiorrhizae may also have some effects. In this article, the pathogenesis of liver injury in AP and its therapy are reviewed.

Structure and biological properties of 2H-1-benzopyran-2-one (coumarin) derivatives

The physicochemical and pharmacological properties of some natural derivatives of 2H-1-benzopyran-2-one (coumarin) have been studied, including decursinol and obtusifol, which are the most promising compounds for practical applications. Using high-resolution 1H and 13C NMR spectra in comparison to the published data, the structure of obtusifol is finally established. Decursinol exhibited the most pronounced antiarrhythmic activity on the model of calcium-chloride-induced arrhythmia in rats: in a doze of 0.5 mg-kg, this compound prevented the loss of experimental animals and restored the sinusoidal rhythm in 100% of cases. The therapeutic antiarrhythmic index (AI = LD50/ED50) of decursinol (AI = 470) significantly exceeds the values for well-known drugs such as quinidine, novocainamide, and lidocaine (AI = 16.5, 17.0 and 22.2, respectively). The antiarrhythmic activity of campestrinol and obtusifol was close to that of decursinol. It was found that obtusifol, decursinol, diumancal, and their analogs (representing calcium ion antagonists of the new generation) significantly influence the potential-dependent conductivity of calcium channels not only of the L-type (encountered in muscles, heart and vessels), but also of the N-and T-types, most widely distributed in the central nervous system and ganglion.

Theoretical Elucidation of Structure-Antioxidant Activity Relationships for Thiazolidinone Derivatives

Thiazolidinone Derivatives (TD) are a novel class of calcium ion (Ca2+) antagonists possessing both Ca2+ overload inhibition and antioxidant activity. The free radical scavenging activity of TD play a key role in its cardioprotective processes. To elucidate the structure-antioxidant activity relationships (SAAR) for TD, a series of phenolic analogues of TD were constructed by adding various substituents to phenol step by step. And the theoretical parameter characterizing the free radical scavenging activity, O–H bond dissociation energy (BDE), was calculated for these phenols by quantum chemical method AM1/B3LYP/6-31G**. Thus, the contribution of each substituent to the O–H BDE was obtained. As a result, not only the SAAR for TD was explained, but also the understanding on TD's antioxidative mechanism was deepened.

The paradoxical toxic effect and antagonism to calcium ions of O-(N-arylcarbamoylated) acylhydroximoyl chlorides exhibiting anticholinesterase action

Carbamoylated oximes of the formula RR1NC(O)ON=C(Cl)R2, N-aryl-containing carbamates exhibit higher antiacetylcholinesterase activity and lower acute toxicity (with a paradoxical dose dependence of the lethal effect) than their N-alkyl analogs. In experiments on isolated guinea pig ilea. the N-aryl carbamates. unlike their N-alkyl-substituted derivatives, were shown to be calcium ion antagonists. The cause of the paradoxical toxic effect of the N-aryl-containing carbamates and their low toxicity in the high dose range is assumed to be a calcium-blocking action.

The effect of calcium ion channel blockers on sperm fertilization potential

To evaluate the effects of calcium ion (Ca2+) channel blockers on male fertility potential. A case comparison of the surface expression of mannose-ligand receptors on motile spermatozoa from 10 known fertile males and from 10 normospermic men taking Ca2+ channel blockers who were seeking infertility treatment. Examination of the effects of in vitro exposure of sperm from fertile donors (n = 14) to antihypertensive medications. Patients from a successful university hospital-based IVF-assisted reproductive technology program and from a male urology private practice. Prescription of alternate hypotensive medications for four male patients; cholesterol loading and unloading in vitro of fertile donor sperm. Motile sperm were tested for their ability to bind fluorescein isothiocyanate-labeled, mannosylated bovine serum albumin as an index of the surface expression of mannose-ligand receptors associated with fertility potential. Acrosome status was simultaneously evaluated by fluorescence microscopy with rhodamine-labeled Pisum sativum lectin. Sperm were assayed before and after an 18-hour or 3-day incubation under capacitating conditions in vitro. Motile spermatozoa of normospermic men taking calcium antagonists for hypertension control do not express head-directed mannose-ligand receptors at high frequency, nor do they undergo spontaneous acrosome loss. Unexpectedly, mannose-ligand receptor translocation from the subplasmalemmal space over the acrosome to the sperm surface and aggregation over the equatorial-postacrosomal regions occurred in acrosome-intact sperm. This differs from fertile controls in whom receptor translocation to the equatorial-postacrosomal segment is coupled with the acrosome reaction (AR). Discontinuation of calcium antagonists results in complete recovery of parameters associated with sperm fertilizing potential: time-dependent increases in the percentages of spermatozoa exhibiting surface mannose-ligand binding and spontaneous ARs in vitro. The effects of in vivo administration of calcium antagonists is mimicked in control fertile donor sperm by inclusion of a Ca2+ channel blocker in the media employed during capacitating incubations. Therapeutic administrations of calcium antagonists for hypertension control cause reversible male infertility associated with an IVF failure. A mechanism of inhibition of sperm fertilizing potential through insertion of lipophilic calcium ion antagonists into the lipid bilayer of the sperm plasma membrane is consistent with our in vitro studies.

Felodipine‐induced gingival hyperplasia: a clinical and histologic study

This paper reports, for the first time, gingival hyperplasia in a patient treated with felodipine, a drug which belongs to the group of calcium ion antagonists. The observed gingival overgrowth was most significant in the area of interdental papillae of the anterior region of the mouth. The described hyperplastic tissue was characterized by a firm and pale appearance, with a normally stippled pattern. Histopathologically, a conspicuous increase of fibrous connective tissue, as well as an inflammatory infiltrate and hyperplasia of the overlying epithelium were observed. Consequently, the present observation adds another drug to the list of substances capable to induce gingival hyperplasia.