scholarly journals Synthesis and vasodilator activity of 3,4-dihydropyrimidin-2(1H)-ones bearing urea, thiourea, and sulfonylurea moieties

2019 ◽  
Vol 97 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Tahir Habila ◽  
Mebrouk Belghobsi ◽  
Mohamed-Zakaria Stiti ◽  
Eric Goffin ◽  
Pascal de Tullio ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Vasodilator Agents ◽  
Biological Models ◽  
Urea Derivatives ◽  
Thiourea Derivatives ◽  
Voltage Gated ◽  
Vasodilator Activity ◽  
Potent Vasodilator

A series of novel 3,4-dihydropyrimidin-2(1H)-ones bearing urea, thiourea, and sulfonylurea moieties were synthesized and pharmacologically evaluated as vasodilator agents. The most interesting vasodilators were the thiourea derivatives 6a and 6b and the urea derivatives 6f–6i and 7f–7h, although the ureas were relatively more active than thioureas. Twenty-fold more active than diazoxide, the urea 6g was the most potent vasodilator (EC50 = 0.983 ± 0.061 μmol/L) and proved to act as a voltage-gated calcium channel blocker. The lack of activity of sulfonylureas, 6k and 7j, could be attributed to their partial ionization at the physiological pH because of their acidic character. It should be interesting to investigate a larger number of compounds, including N-methylated sulfonylureas, to increase the vasodilator activity and to explore other biological models.

scholarly journals Weaver granule neurons are rescued by calcium channel antagonists and antibodies against a neurite outgrowth domain of the B2 chain of laminin.

1996 ◽  
Vol 134 (2) ◽  
pp. 477-486 ◽  
Author(s):  
P Liesi ◽  
J M Wright
Keyword(s):  
Calcium Channel ◽  
Neurite Outgrowth ◽  
Calcium Channel Blocker ◽  
Neuronal Migration ◽  
Channel Blocker ◽  
Postnatal Life ◽  
Granule Neurons ◽  
Mk 801 ◽  
Voltage Gated ◽  
High Concentrations

The weaver mutation impairs migration of the cerebellar granular neurons and induces neuronal death during the first two weeks of postnatal life. To elucidate the molecular mechanisms for the impaired neuronal migration, we investigated the rescue mechanisms of the weaver (wv/wv) granule neurons in vitro. We found that Fab2 fragments of antibodies against a neurite outgrowth domain of the B2 chain of laminin enhanced neurite outgrowth and neuronal migration of the weaver granule neurons on a laminin substratum and in the established cable culture system. The rescue of the weaver granule neurons by antibodies against the B2 chain of laminin may result from the neutralizing effect of these antibodies against the elevated B2 chain levels of the weaver brain. The L-type calcium channel blocker, verapamil (1-5 microM), also rescued the weaver granule neurons. High concentrations of MK-801 (10-20 microM), a glutamate receptor antagonist and voltage-gated calcium channel blocker, rescued the weaver granule neurons similar to verapamil, but low concentrations of MK-801 (1 microM) had no rescue effect. Simultaneous patch-clamp studies indicated that the weaver granule neurons did not express functional N-methyl-D-aspartate receptors further indicating that the rescue of the weaver granule neurons by MK-801 resulted from its known inhibition of voltage-gated calcium channels. The present results indicate that antibodies against the B2 chain of laminin, verapamil, and high concentrations of MK-801 protect the weaver granule neurons from the otherwise destructive action of the weaver gene. Thus, both the laminin system and calcium channel function contribute to the migration deficiency of the weaver granule neurons.

Chronic treatment by the calcium channel blocker ± PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo

1990 ◽  
Vol 122 (3) ◽  
pp. 403-408
Author(s):  
Ph. Touraine ◽  
P. Birman ◽  
F. Bai-Grenier ◽  
C. Dubray ◽  
F. Peillon ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Plasma Prolactin ◽  
Estradiol Treatment ◽  
Kinase C ◽  
Protein Kinase C Activity

Abstract In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with ± PN 200-110 (3 mg · kg−1 · day−1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 ± 4.9 vs 95.0 ±9.1 μg/l, p<0.0001) and pituitary weight (19.9 ± 0.4 vs 23.0 ± 0.6 mg, p <0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.

Effects of an Antihypertensive Combination in Japanese Hypertensive Outpatients Based on the Long-Acting Calcium Channel Blocker Benidipine on Vascular and Renal Events: A Sub-Analysis of the COPE Trial

2020 ◽  
Vol 16 ◽  
Author(s):  
Seiji Umemoto ◽  
Toshio Ogihara ◽  
Masunori Matsuzaki ◽  
Hiromi Rakugi ◽  
Kazuyuki Shimada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Rank Test ◽  
Vascular Events ◽  
Treatment Groups ◽  
Β Blocker ◽  
The Difference ◽  
Long Acting

Background: In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events) three benidipine (a calcium channel blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40–85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional angiotensin receptor blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group. Objective and Methods: We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients. Results: A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events p=0.92 renal events p=0.16 log-rank test. Conclusions: Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there is no enough these events to compare the difference in the three treatment groups.

scholarly journals Author Correction: Calcium channel blocker amlodipine besylate therapy is associated with reduced case fatality rate of COVID-19 patients with hypertension

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Lei-Ke Zhang ◽  
Yuan Sun ◽  
Haolong Zeng ◽  
Qingxing Wang ◽  
Xiaming Jiang ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Case Fatality Rate ◽  
Channel Blocker ◽  
Case Fatality ◽  
Fatality Rate ◽  
Amlodipine Besylate

A Correction to this paper has been published: https://doi.org/10.1038/s41421-021-00267-0

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