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Cardiovascular effects of CPU‐23, a novel L‐type calcium channel blocker with a unique molecular structure
Author(s) -
Dong Hui,
Earle Mary L.,
Jiang Yanfen,
Loutzenhiser Kathy A.,
Triggle Christopher R.
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701508
Subject(s) - contraction (grammar) , diltiazem , chemistry , phenylephrine , extracellular , channel blocker , calcium , medicine , blood pressure , biochemistry
1 The cardiovascular effects of CPU‐23 (1‐{1‐[(6‐methoxy)‐naphth‐2‐yl]}‐ethyl‐2‐(1‐piperidinyl)‐acetyl‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline), a cleavage product of tetrandrine, were investigated using the whole cell perforated patch‐clamp technique, in vitro tension measurements and in vivo haemodynamic recordings. 2 CPU‐23 (1 and 10 μ M ) dose‐dependently reduced concentration–response curves for KCl and phenylephrine (PE) in the rat tail artery; inhibition of KCl‐induced contraction was much more potent than for PE. At the same concentrations, CPU‐23 inhibited the inward Ba 2+ currents in single smooth muscle cells isolated from the rat tail artery, while CPU‐23 (10 μ M ) produced 95% vasorelaxation of the rat middle cerebral artery preconstricted with BayK 8644. 3 CPU‐23 (10 and 30 μ M ) inhibited the noradrenaline‐induced phasic contraction of the rat tail artery in the absence of extracellular Ca 2+ from 40% of control to 23% and 14%, respectively ( P <0.01) and tonic contraction of the artery after addition of Ca 2+ (2 m M ) from 100% of control to 83% and 75%, respectively ( P <0.01). In the presence of extracellular Ca 2+ the PE‐induced contraction was reduced by CPU‐23 (30 and 100 μ M ) to 27% and 37%, respectively. 4 The haemodynamic profile of CPU‐23 in the rat was very similar to diltiazem. At 5 mg kg −1 CPU‐23 induced a rapid onset and long‐lasting decrease in left ventricular systolic pressure (LVSP), maximal velocity of pressure increase ( dP/dt max ), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). When haemodynamic actions of CPU‐23, verapamil, diltiazem and nifedipine were compared at equidepressor doses, the order of potency for reducing LVSP and dP/dt max was verapamil > CPU‐23 = diltiazem > nifedipine and the order of potency for decreasing HR was verapamil = CPU‐23 = diltiazem > nifedipine. 5 These data indicate that CPU‐23 is a novel calcium channel blocker with unique molecular structure, which exerts antihypertensive and cardiac depressant effects due primarily to its action on L‐type voltage‐gated calcium channels.