The interaction of calcium antagonists (slow channel blockers) with myocardial alpha adrenoceptors

Section: Discussionmentioning

confidence: 74%

Effects of diltiazem on calcium concentrations in the cytosol and on force of contractions in porcine coronary arterial strips

Hirano

Kobayashi

Abe

et al. 1990

“…Neither verapamil nor nimodipine displaced [3HJ-naloxone from its binding sites and therefore they are probably not active at the level of the opioid receptor. Furthermore, while verapamil seems to be able to increase NA release both in brain and peripheral tissues (Galzin & Langer, 1983;Zsoter et al, 1984) and to interact with NA receptors (Nayler et al, 1982;Galzin & Langer, 1983), nimodipine (1Omg kg' i.v.) does not alter the brain NA content or metabolism and at a concentration of IO-' M does not interact in vitro with the actions ofNA (Towart et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Calcium channel inhibitors suppress the morphine‐withdrawal syndrome in rats

Bongianni

Carlà

Moroni

et al. 1986

139

1 The effects of the Ca2"-channel blockers verapamil and nimodipine, on the behavioural signs of naloxone (1 mg kg-')-induced abstinence syndrome in morphine-dependent rats, were evaluated. The content of noradrenaline (NA) and of its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) was measured, using high performance liquid chromatography and electrochemical detection or gas chromatography-mass spectrometry, in various brain regions ofthese animals. Possible interactions of nimodipine and verapamil with opioid receptors were evaluated by examining their ability to displace [3HJ-naloxone binding to brain membranes.2 Verapamil (5, 10 and 50mg kg-')and nimodipine (1, 5and 10mg kg-') dose-dependently reduced most of the signs of morphine abstinence. 3 Naloxone-precipitated abstinence decreased the NA content in the cortex, hippocampus, brainstem and cerebellum. In the same brain regions the content of MHPG increased, suggesting an increased release of the amine during morphine abstinence. 4 Nimodipine (10mgkg-' i.v.) did not change the content of NA or MHPG in the cortex, hippocampus and brainstem. However, nimodipine pre-treatment markedly reduced the changes in NA and MHPG content induced by the abstinence syndrome.5 Neither verapamil nor nimodipine displaced [3H]-naloxone from its binding sites.6 These results suggest that Ca2+-channel blockers suppress the behavioural and neurochemical expressions of morphine abstinence by a mechanism that differs from those of opioids or a2-adrenoceptor agonists.

“…It is interesting that increasing the concentration of diltiazem from 1 to 10 jmol [`caused little further antagonism of NA responses. Higher diltiazem concentrations were not tested since these cause appreciable direct al-adrenoceptor antagonism rather than simply blocking calcium channels (Nayler et al, 1982;Cavero et al, 1983). The effect of 10 pmol Id iltiazem thus probably represents a near maximal effect of blockade of entry of extracellular calcium ion on responses to NA in this vessel, and amounts to 0.9 log unit shift in the NA curve.…”

Section: Discussionmentioning

confidence: 99%

Effects of reduced calcium ion concentration and of diltiazem on vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation in rat isolated tail artery

Medgett

Rajanayagam

1984

1 In isolated, perfused proximal segments of Sprague-Dawley rat tail artery, idazoxan (100 nmol 1-1) displaced the concentration-response curve to noradrenaline (NA) to the right. The log shift of the NA concentration-response curve was greater at lower concentrations than at higher concentrations of NA. Idazoxan (100 nmol 11) had no effect on responses to electrical stimulation.2 Prazosin (10 nmol 1-') displaced the concentration-response curve to NA to the right as well as markedly reducing responses to sympathetic nerve stimulation. 3 The concentration-response curve to NA, obtained after reducing the concentration of calcium ions in the Krebs solution from 2.5 to 0.6 mmol 1-', was significantly displaced to the right. Responses to sympathetic nerve stimulation were not affected by this reduction in the concentration of calcium ions.4 Diltiazem (1 and 10 pimol 11) significantly displaced the concentration-response curve to NA to the right but had no effect on sympathetic nerve stimulation. 5 These in vitro results in peripheral arterial smooth muscle confirm the findings of previous in vivo studies which suggest that aC2-adrenoceptors contribute to the vasoconstrictor responses elicited by cx-adrenoceptor agonists and that these responses but not those mediated by oti-adrenoceptors are dependent on extracellular calcium.