Cardiotropic Activity Research Articles

Modified Coumarins. 4. Synthesis and Biological Properties of Cyclopentaneannelated Furocoumarins

Psoralen and allopsoralen analogs that contain an annelated cyclopentane were synthesized from 7-hydroxyand 9-hydroxy-1,2,3,4-tetrahydrocyclopenta[c]chromen-4-ones. 9-Phenyl-1,2,3,4-tetrahydrocyclopenta[c]furo[3,2-g]chromen-4-one exhibited low toxicity, acted as a CNS stimulant, and exhibited cardiotropic activity.

Cardioacceleratory action of tachykinin-related neuropeptides and proctolin in two coleopteran insect species ☆,☆☆

Several cardioactive peptides have been identified in insects and most of them are likely to act on the heart as neurohormones. Here we have investigated the cardioactive properties of members of a family of insect tachykinin-related peptides (TRPs) in heterologous bioassays with two coleopteran insects, Tenebrio molitor and Zophobas atratus. Their effects were compared with the action of the pentapeptide proctolin. We tested the cardiotropic activity of LemTRP-4 isolated from the midgut of the cockroach Leucophaea maderae, CavTK-I and CavTK-II isolated from the blowfly Calliphora vomitoria. The semi-isolated hearts of the two coleopteran species were strongly stimulated by proctolin. We observed a dose dependent increase in heartbeat frequency (a positive chronotropic effect) and a decrease in amplitude of contractions (a negative inotropic effect). In both beetles the TRPs are less potent cardiostimulators and exert lower maximal frequency responses than proctolin. LemTRP-4 applied at 10 −9–10 −6 M was cardiostimulatory in both species inducing an increase of heart beat frequency. The amplitude of contractions was stimulated only in Z. atratus. CavTK-I and CavTK-II also exerted cardiostimulatory effects in Z. atratus at 10 −9–10 −6 M. Both peptides stimulated the frequency, but only CavTK-II increased the amplitude of the heart beat. In T. molitor, however, the CavTKs induced no significant effect on the heart. Immunocytochemistry with antisera to the locust TRPs LomTK-I and LomTK-II was employed to identify the source of TRPs acting on the heart. No innervation of the heart by TRP immunoreactive axons could detected, instead it is possible that TRPs reach the heart by route of the circulation. The likely sources of circulating TRPs in these insects are TRP-immunoreactive neurosecretory cells of the median neurosecretory cell group in the brain with terminations in the corpora cardiaca and endocrine cells in the midgut. In conclusion, LemTRP-4, CavTK-I and CavTK-II are less potent cardiostimulators than proctolin and also exert stimulatory rather than inhibitory action on amplitude of contractions. The differences in the responses to proctolin and TRPs suggest that the peptides regulate heart activity by different mechanisms.

Peptide TSKY Decelerates Outcome of the Ground Squirrel from Hibernation

Effect of peptide TSKY on the heart rate was studied in the ground squirrel Citellus undulatus at outcome from hibernation. At provocation of awakening in the first half of the hibernation bout (the 3rd–4th hibernation days), an intraperitoneal peptide injection at a dose of 1 mg/kg produced a deceleration of the HR increase and elongated the time of transfer of the animal to the normothermia state. This effect was not observed in the second half of the hibernation bout (the 5th–7th hibernation days). The study of the peptide cardiotropic activity on an isolated frog heart did not reveal any statistically significant TSKY activity.

Cardiotropic activity of estrogens during hormone replacement therapy in postmenopausal women

Cardiotropic activity of estrogens after a single administration and during 12-week substitute hormone therapy was studied during echocardiography and Doppler echocardiography in estrogen deficient women with natural or surgical postmenopause with negative cardiovascular (vasomotor) symptoms with hyperkinetic central hemodynamics, high arterial pressure, and disordered diastolic function of the left ventricle. The results confirm the cardioprotective and positive hemodynamic activity of substitute estrogens. Estrogens improved the initially disturbed diastolic and systolic function of the left ventricle, moderately decreased heart rate and systolic and diastolic arterial pressure. Time course of cardioprotective and hemodynamic effects of substitute monoestrogen therapy and estrogen/gestagen hormone therapy was virtually the same.

Comparative study of antiarrhythmic effects of methacizin and its components under conditions of neurogenic atrial fibrillation

Antifibrillatory effect of methacizin under conditions of neurogenic atrial fibrillation in cats was due to its vagolytic rather than cardiotropic activity. The immediate antifibrillatory effect of methacizin surpassed that of its components (ethacizin and ethmozin). However, 30 min after administration the antiarrhythmic effect of methacizin did not differ from that of ethacizin alone.

The role of neurotropic component in therapeutic effect of antiarrhythmic drugs

Acute experiments on anesthetized cats with neurogenic atrial fibrillation showed that the antifibrillatory effect of procainamide, lidocaine, and ethacizin correlated with their vagolytic rather than with cardiotropic activity.

Antiarrhythmic activity of amiodarone in neurogenic atrial fibrillations

Acute experiments on cats showed that dynamics of amiodarone antiarrhythmic activity with respect to neurogenic atrial fibrillations correlates with its neurotropic effects rather than its cardiotropic activity.

New proctolin analogues: Synthesis and biological investigation in insects

We have extended our work on structure/activity relationship studies of the neuropeptiden proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH) by evaluating the effects of the following proctolin analogues: H-X1-Tyr-Leu-Pro-Thr-OH, where X1 = D-Arg (I), N-Me-Arg (II), Can (III), Orn(di-Me) (IV), Orn(iPr) (V), Lys(N, N-di-Me) (VI), Lys(iPr) (VII), Lys(Nic) (VIII) and D-Lys(Nic) (IX). In analogues I–IX, the N-terminal Arg residue was replaced by basic amino acid derivatives with peptides containing amino acid residues with an isosteric system on the back side chain relative to Arg (compounds III, V and VI) or homo-Arg (compound VII). Analogues I–IX were evaluated for myotropic activity on the in vitro heart preparation of Tenebrio molitor, whereas peptides II, V, and VII–IX were tested for contractile activity on the isolated foregut of locust Schistocerca gregaria. Peptide II and III showed full cardiotropic activity in T. molitor while peptides V and VII showed 40% and 15%, respectively, locust-gut contracting activity of proctolin.

Comparative evaluation of the inotropic effect of lipophilic and hydrophilic forms of 17P-estradiol and progesterone

Changes in the contractility under the effect of lipophilic and hydrophilic 17^-estradiol and progesterone were studied on an isolated atrial auricula. The hydrophilic forms of female sex steroids possessed a higher cardiotropic activity than their lipophilic analogs. Lipophilic 17^-estradiol suppressed, whereas the hydrophilic form boosted the contractile function of the isolated rat atrium. Progesterone depressed cardiac contractility, no matter which forms were used.

Diterpenoid alkaloids as a new class of antiarrhythmic agents. Structure-activity relationship

The cardiotropic activities of 111 diterpene alkaloids and their synthetic derivatives having lycoctine, heteratisine, napelline, and denudatine skeletons have been studied. It has been established that the overwhelming majority of these compounds exhibit a pronounced antiarrhythmic and antifibrillatory action, which is a finding of practical interest. Their structure-activity relationships — the directions of their action in relation to the results of x-ray structural analysis — have been investigated. The following have been selected and proposed as antiarrhythmic agents for practical medicine: lappaconitine, deacetyllappaconitine, 6-benzoylheteratisine, 14-benzoyl talatisamine, 1-benzoylnapelline, and others. Of them, lappaconitine hydrobromide (allapinin) has been introduced into public health practice.

A water-soluble form of estradiol with estrogenic and cardiotropic activity

It is demonstrated that a water-soluble form of estradiol (disodium salt of estradiol diphosphate), apart from having an estrogenic influence on the uterus, is effective against severe blood loss and has a cardiotropic actiity.

ChemInform Abstract: Synthesis and Cardiotropic Activity of New Derivatives of the Two Stereoisomers of 1‐(2‐(3,4‐Dimethoxyphenyl)ethyl)‐2‐methyl‐4‐ethynyl‐4‐hydroxy‐trans‐decahydroquinoline.

AbstractThe ethynyldecahydroquinolinole (I) is transformed into the derivatives (II), (III), (IV), and (VII) by common methods.

ChemInform Abstract: Synthesis and Cardiotropic Activity of Stereoisomeric 1‐(2‐(3,4‐Dimethoxyphenyl)ethyl)‐2‐methyl‐4‐ethynyl‐4‐acyloxy‐trans‐decahydroquinolines.

AbstractThe carbinols (I) are coupled with the carboxylic chlorides (II) or (IV) to give the esters (III).

Studies on the Preparation and Biological Activities of 3‐(O‐Methoxybenzyl)Sydnone Derivatives and 3‐(Fluorophenyl)Sydnones

AbstractTwo new sydnones; 3‐(o‐methoxybenzyl)sydnone(1) and 3‐(o‐melhoxybenzyl)‐4‐morpholinomethylsydnone(2) were synthesized from o‐methoxybenzylamine and ethyl bromoacetat in moderate yields.3‐(o‐,m‐,p‐Fluorophenyl)sydnones were prepared from the corresponding fluoroaniline and chloroacetic acid in higher yields with a conventional method.From the biological activity test, 1 shows significant response of coronary dilation test, collagen induced platelet aggregation inhibition, local anesthetic and moderate cardiotropic activity. In addition, 1 also leads to anticonvuls, muscle relaxation and behavior depression. But 2 only shows inhibition of collagen induced platelet aggregation and antiwrithing.3‐(p‐Fluorophenyl)sydnone (5) shows significant response of coronary dilation, collagen induced platelet aggregation inhibition, moderate cardiotropic activity, antiwrithing and local anesthetic But 3‐(o‐Fluorophenyl)sydnone(3) and 3‐(m‐fluorophenyl)sydnone(4) only show coronary dilation and moderate cardiotropic activity.

Secoiridoid glycosides from Jasminum multiflorum

In addition to 10-hydroxyoleuropein and 10-hydroxyligustroside, three new secoiridoid glycosides, multifloroside, multiroside, and 10-hydroxyoleoside-11-methyl ester have been isolated from the water soluble fraction of Jasminum multiflorum. Their structures were established by spectroscopic analyses and chemical correlations. 10-Hydroxyoleuropein and multifloroside were found to possess coronary dilating and cardiotropic activities.

Cardiotropic activity of pyridin-2(1H)-ones

Cardiotropic activity of pyridin-2(1H)-ones

Novel secoiridoid lactones from Jasminum multiflorum.

Four new secoiridoid lactones, jasmolactones A [1], B [2], C [3], and D [4], were isolated from the aerial part of Jasminum multiflorum. The structures of these compounds, which contain a novel bicyclic 2-oxo-oxepano[4,5-c]pyran ring system, were established by spectral analyses and chemical correlations. Pharmacological testing revealed that jasmolactones B and D possess coronary vasodilating and cardiotropic activities.

Synthesis and cardiotropic activity of new derivatives of two stereoisomers of 1-[2-(3,4-dimethoxyphenyl)ethyl]-2-methyl-4-ethynyl-4-hydroxyl-trans-decahydroquinoline

Synthesis and cardiotropic activity of new derivatives of two stereoisomers of 1-[2-(3,4-dimethoxyphenyl)ethyl]-2-methyl-4-ethynyl-4-hydroxyl-trans-decahydroquinoline

Synthesis and cardiotropic activity of stereoisomeric 1-[2-(3,4-dimethoxyphenyl) ethyl]-2-methyl-4-ethynyl-4-acyloxy-trans-decahydroquinolines

We have previously [2] described the synthesis of the trans isomer (I) of l-[2-(3,4-dimethoxyphenyl)ethyl]-2-methyl-4-ketodecahydroquinoline and the two acetylenic alcohol isomers (II and III) corresponding to it. It was shown that II has pronounced spasmolytic activity. In order to study their new cardiotropic properties and the effect of the nature of the ester group on the pharmacological activity in the present paper we have developed a method for obtaining the acetate and benzoate esters on the basis of the individual isomers II and III and have studied their cardiovascular action.

Activité comparée des hormones juvéniles en C-18 (JH-I) et en C-16 (JH-III) chez Locusta migratoria

The comparative activity of C-16 and C-18 juvenile hormones is studied in Locusta migratoria on four well-known physiological functions of the corpora allata by means of a single injection of a solution of hormone in oil at doses of 50, 100, and 200 μg/animal. Judged on morphogenesis and pigmentation, JH-I (C-18 JH) as well as JH-III (C-16 JH) show a real juvenilizing effect. The potency of JH-I is much higher than that of JH-III because the first hormone only produces supernumerary larvae and most modified green animals. JH-I counterbalances exactly the lack of CA on the gonadotropic function whereas JH-III allows only about 50 per cent development of oöcytes. The cardiotropic activity of JH-I is similar to that of the CA. The C-18 juvenile hormone is until now the only studied ‘juvenilizing’ compound which increases the heartbeat. JH-III appears to have no noticeable effect on the heart. These results combine to prove that only JH-I has an activity similar to the Locusta corpora allata on morphogenesis, pigmentation, ovarian maturation, and the cardiac activity of L. migratoria.