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PubMed1995

Effects of a calcium channel blocker, manidipine hydrochloride, on the regulatory mechanism of glomerular capillary pressure in SHR.

In an attempt to clarify whether glomerular capillary pressure (Pgc) in hypertension can be reduced by a calcium channel blocker (CaB), renal clearance and micropuncture experiments were carried out on male heminephrectomized spontaneously hypertensive rats (SHR; n = 15). Renal circulatory parameters (RBF and GFR) and proximal tubular stop flow pressure (Psf) were measured during the control period, during manual aortic clamping, and after administration of manidipine hydrochloride (MDP, 10 micrograms/kg body weight in bolus). Because Psf only represents Pgc during zero tubular flow, the responsiveness of tubulo-glomerular feedback (TG feedback) was also assessed to obtain the "steady state Pgc", an operating point in each experimental period. Administration of MDP decreased systemic blood pressure (SBP) and renal vascular resistance (RVR), but increased renal blood flow (RBF) significantly. Psf decreased following the administration of MDP (33.65 +/- 1.45 mmHg), reaching a lower level than during aortic clamping (39.93 +/- 2.37 mmHg) or in the control period (50.78 +/- 2.73 mmHg). TG feedback responsiveness was attenuated during clamping, and was incompletely inhibited by MDP, whereas the operating point (29.3 mmHg) was lower than during clamping (32.9 mmHg) or in the control period (41.0 mmHg). The stability of RBF during the alteration of renal perfusion pressure (RPP) was not abolished by MDP. From these results, we suggest that MDP significantly decreases Pgc in the steady state not only by the reduction of RPP, but also by the amelioration of renal microcirculation.

Animals↗
PubMed1994

Influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats.

The present study was designed to assess the influence of treatment with the calcium channel blocker darodipine (PY 108-068) on the morphology of pial and coronary arteries in spontaneously hypertensive rats (SHR). Twelve week male SHR were used in this study. One group was treated with a daily dose of 5 mg/Kg of darodipine, while the control group of SHR was treated with placebo. Age-matched normotensive Wistar Kyoto (WKY) rats were used as a reference group. After 12 weeks of treatment the rats were sacrificed. The brains and the hearts were removed, embedded in resin, cut and used for light microscope analysis. Darodipine treatment reduced blood pressure in SHR. Morphometric analysis of different sized pial and coronary arteries revealed decreased arterial lumen in SHR in comparison with WKY rats. The area occupied by the tunica media and the media-to-lumen ratio were increased in SHR in comparison with WKY rats. In darodipine-treated rats the area occupied by the arterial lumen was increased in comparison with control SHR, whereas the area occupied by the tunica media and the media-to-lumen ratio were decreased. Pial arteries were more sensitive than coronary arteries to darodipine treatment. Medium and small sized pial and coronary arteries were most sensitive to darodipine treatment. Large-sized coronary artery branches were unaffected by pharmacological treatment. The above results suggest that treatment of SHR with darodipine is able to reduce high blood pressure and to counter the development of structural changes of pial and coronary arteries noticeable in SHR. The higher sensitivity of the cerebral vasculature to darodipine treatment is discussed.

Animals↗
PubMed1992

[Calcium channel blockers inhibit human low-density lipoprotein peroxidation induced by oxygen free radicals in vitro].

Previous studies have shown that calcium-antagonists may reduce the development of experimental atherosclerosis, and that nifedipine may slow progression of coronary atherosclerosis in man. The mechanisms responsible for this effect are still unclear. It has been recently proposed that oxygen-free radicals can induce peroxidation of human low-density lipoproteins (LDL), and that peroxidized LDL may be an atherogenic stimulus. Chemical modified LDL are internalized by macrophages via specific cell surface receptor that was termed the scavenger receptor, and could induce foam cells transformation in vivo. Previous studies on other systems have shown that calcium-antagonists may effectively inhibit oxygen radical-induced lipid peroxidation. These drugs, though differing widely in their chemical structure, are lipophilic to various degrees and presumably would concentrate in the lipid domain of the phospholipid-rich membranes. Therefore, the aim of the present study was to investigate whether calcium-channel blockers may reduce human LDL peroxidation. Purified human LDL were exposed to oxygen radicals generated by xanthine-xanthine oxidase (18 hours) after a pre-incubation (30 min) in presence of different concentrations of nifedipine, diltiazem and verapamil. Peroxidation was measured from malonyldialdehyde production. The results show that calcium-antagonists prevent LDL peroxidation. Thus, calcium-antagonists may reduce peroxidation of human LDL in vitro, at clinically relevant concentrations. These data suggest that reduced formation of atherogenic peroxidized LDL may be an additional mechanism for the anti-atherosclerotic effects of calcium-antagonists in vivo.

Arteriosclerosis↗
PubMedDate not supplied

Long-term patient compliance with prescribed regimens of calcium channel blockers.

Patient compliance with drug therapy is an important component in the successful management of chronic diseases. The objective of this study was to determine the mean compliance ratio for calcium channel blocking agents in a 2-year study of prescription claims records. The effect on compliance relating to the number of daily doses, length of drug therapy, therapeutic use, and patient age also was investigated. We analyzed prescription drug claims records from an insurance program with prescription drug benefits for state employees, teachers, and retirees in the state of Oklahoma. A total of 105,559 calcium channel blocker prescription claims representing 9807 treatment regimens were made between July 1990 and June 1992. A stratified random sample of 2377 treatment regimens was drawn from this population. The mean compliance ratio for all patients was 78.22%. The number of daily doses and the length of the treatment regimen were significant factors in the compliance model (P = 0.0001). The age of the patient was not significant. Differentiating therapeutic use by symptomatic (angina pectoris) or nonsymptomatic (hypertension) indications also was not significant. Once-daily treatment regimens were found to provide the highest mean compliance ratio (84.86%). This was followed by twice-daily administration, with a mean of 79.88%; three times daily, 75.16%; and four times daily, 73.06%. Multiple comparisons analysis indicated a statistically significant difference between each dosing regimen with the exception of three-versus four-times-daily administration. The highest mean compliance ratio (101.51%) was found with treatment lengths of 2 months. The mean compliance ratio declined as the length of therapy increased. The decline in patient compliance was most pronounced with treatment lengths between 2 and 4 months. The mean compliance ratio was lowest for treatment lengths of 16 months (71.00%), although there was no significant difference between treatment lengths of 6, 12, 16, or 20 months. The deterioration of compliance over time ceased with treatment lengths exceeding 16 months. Based on these data, prescribers should attempt to minimize or simplify the frequency of the dosing regimen when possible. Discussions with the patient involving medication compliance may be of greater value during follow-up visits with the physician or pharmacist when noncompliant behavior becomes most pronounced.

Aged↗
PubMed1999

Use of calcium-channel blockers in pediatric renal transplant recipients.

Hypertension (HTN) is a significant problem in pediatric renal transplant (TP) recipients, predisposing the individuals to the development of cardiovascular disease and graft dysfunction. Calcium channel blockers (CCB) are considered excellent agents to treat post-TP HTN. We compared the efficacy and adverse effects of the two most commonly prescribed CCBs in our pediatric renal TP population: nifedipine (Procardia, or P) and amlodipine (Norvasc, or N). All patients (n = 24) had been started on a CCB for systolic (SBP) and/or diastolic BP (DBP) > 95%. There were no other changes in adjunctive antihypertensive medications or doses during the cross-over period. Post-TP, pretreatment (pretx) SBP was 137.6 +/- 10.9 mmHg. The post-treatment SBP were (in mmHg): 128.5 +/- 11.9 (all patients, n = 24) (p = 0.009 vs. pretx); 126.4 +/- 10.0 (P alone, n = 15) (p = 0.007 vs. pretx); 132.8 +/- 14.4 (P + other antihypertensive(s), n = 9) (p = 0.331, NS vs. pretx). The post-TP, pretreatment DBP was 88.2 +/- 11.1 mmHg. The post-treatment DBP were (in mmHg): 78.5 +/- 6.9 (all patients, n = 24) (p = 0.03 vs. pretx); 77.2 +/- 7.4 (P alone, n = 15) (p = 0.008 vs. pretx); 80.7 +/- 6.1 (P + other antihypertensive(s), n = 9) (p = 0.063, NS vs. pretx). P and N were equally effective in reducing SBP (p = 0.843, NS) and DBP (p = 0.612, NS). Cyclosporin A (CyA) dose (p = 0.81) and trough levels (p = 0.19) were similar in P- and N-treated patients. Calculated GFR was virtually identical in P- and N-treated patients (p = 0.89). Patients (or parents of) reported a higher incidence of various side-effects while receiving P, including headache, flushing, dizziness and leg cramps. Furthermore, 22/24 (91.7%) reported some degree of gingival hyperplasia during treatment with P, and all these patients reported a stabilization or reduction of hypertrophy after the switch from P to N. We conclude that CCBs (N) are efficacious drugs for the purpose of BP control and renal protection in pediatric renal TP recipients.

Adolescent↗
PubMedDate not supplied

Effects of calcium channel blockers on cultured rat embryos.

Gestational day 11 rat embryos were cultured for 20 h in the presence of nifedipine (NIF), diltiazem (DIL) and verapamil (VER), and the effects of these calcium channel blockers on embryonic heart rate and gross morphology were examined. Reductions of embryonic heart rate were dose dependent and reversible. Effects on the heart rate were seen at doses as low as 0.3, 1 and 20 micrograms ml-1 for VER, DIL and NIF, respectively. Retardation of embryonic growth and morphological abnormalities, which were related to circulation defects, were seen at termination. The minimum doses to produce 100% effect on gross morphology were 2, 6 and 40 micrograms ml-1 for VER, DIL and NIF, respectively. These findings suggest that embryolethality seen in vivo studies is partly due to circulation defects and the associated morphological abnormalities in rats.

Animals↗
PubMed2000

[A case of primary aldosteronism presenting hypokalemic myopathy induced by benidipine hydrochloride; a dihydropyridine calcium channel blocker].

We report a 46-year-old man with primary aldosteronism presenting hypokalemia, periodic paralysis and hypokalemic myopathy whose clinical course paralleled with the dosage of benidipine hydrochloride, a dihydropyridine calcium channel blocker (DHP-CCB), administered for the treatment of hypertension. To see relations between DHP-CCB and episodes of motor weakness in patients with primary aldosteronism, we surveyed retrospectively the history of motor weakness and anti-hypertensive drugs in 14 consecutive cases with primary aldosteronism in our institute. Five patients out of 11 cases (45.5%) who had received DHP-CCB experienced muscle weakness, however, the rest of three patients receiving other anti-hypertensive drug had not experienced weakness. Though, less attention has been paid as thiazide diuretics, it is reported that DHP-CCB also induces hypokalemia through several mechanisms. However, the occurrence of motor weakness by DHP-CCB is very rare. Our results show that primary aldosteronism should be taken into account when we encounter patients manifesting episodic motor weakness by the use of DHP-CCB.

Calcium Channel Blockers↗
PubMed2001

Central sympathoinhibitory effects of calcium channel blockers.

It is generally assumed that the arterial vasodilation induced by inhibition of Ca(2+) influx into vascular smooth muscle cells represents the main mechanism for the hypotensive effect of dihydropyridine calcium channel blockers. Increases in sympathetic tone have been related to activation of the arterial baroreflex by rapid lowering of blood pressure. This review highlights new findings in two areas. First, in animal studies, direct central administration of dihydropyridines such as nifedipine or amlodipine lowers sympathetic nerve activity and thereby blood pressure. Peripheral administration of nifedipine or amlodipine at low rates appears to result in gradual accumulation of drug in the central nervous system, and also causes lowering of sympathetic nerve activity and thereby lowering of blood pressure (rather than by arterial vasodilation). Second, in hypertensive humans treated with long-acting dihydropyridines and presumably little activation of the arterial baroreflex, some studies have demonstrated lowering of sympathetic activity (as assessed by plasma norepinephrine), but others reported increases (as assessed by plasma norepinephrine or microneurography). This sympathoexcitatory response may be due to activation of the renin-angiotensin system, particularly at higher doses.

Animals↗
PubMed1990

Effects of the novel coronary selective calcium channel blocker, McN-6186, on cardiocirculatory dynamics, coronary vascular resistance, and cardiac output distribution in normal, conscious rats.

The purpose of this study was to characterize the cardiocirculatory effects of the novel calcium channel blocker, McN-6186 (McN), normal, conscious rats. Animals were instrumented under halothane anesthesia for right atrial, left ventricular, arterial, and venous pressure recordings. The radioactive microsphere technique was used to measure regional blood flow (RBF) and cardiac output (CO) before (control) and during intravenous (i.v.) infusion of either McN at three doses (0.03, 0.1, 0.3 mg/kg) or vehicle at an equal infusion rate (0.0408 ml/min). Nifedipine (NIF) was also studied at three similar blood pressure (BP)-lowering doses (0.025, 0.150, and 0.375 mg/kg). The predominant effect of McN in conscious rats was to cause coronary vasodilation. The coronary vasodilator potency of McN was similar to NIF (ED25, McN = 0.03 mg/kg, NIF = 0.025 mg/kg). Neither McN nor NIF significantly changed systemic vascular resistance (SVR) over their respective coronary vasodilator dose ranges, suggesting that both compounds are selective coronary vasodilators. The doses of McN and NIF that reduced mean arterial pressure (MAP) by 25% (ED25) were similar (McN = 0.3 mg/kg, NIF = 0.375 mg/kg). At equal BP-lowering doses, McN increased coronary flow by 145% versus 110% for NIF. McN did not have major effects on other regions of the peripheral circulation. There was, however, some vasodilator activity in the renal and cerebral vascular beds. Because McN reduced coronary vascular resistance at a dose lower than that required to reduce resistance in other vascular beds, this compound appears to be a selective coronary vasodilator and may have therapeutic efficacy as an antianginal agent.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed2005

Parathyroid hormone levels, calcium-channel blockers, and the dyslipidemia of nondiabetic hemodialysis patients.

BACKGROUND: Experimental studies have shown that increased levels of parathyroid hormone (PTH) in uremia may cause elevation of intracellular calcium, predisposing to insulin resistance and lipid metabolism abnormalities. Administration of calcium-channel blockers (CCBs) in these models protects against the development of lipid profile abnormalities. This study evaluates the combined effect of intact PTH (iPTH) levels and administration of CCB on the lipid profiles of nondiabetic hemodialysis patients. METHODS: One hundred and eight non-diabetic hemodialysis patients were studied for 6 months. The population was divided into four groups, according to iPTH levels and administration of CCB: (A) iPTH<70 pg/mL, administration of CCB (n=16), (B) iPTH>300 pg/mL without administration of CCB (n=43), (C) iPTH<70 pg/mL without CCB administration (n=19), and (D) iPTH>300 pg/mL with CCB administration (n=30). Serum concentrations of total cholesterol, high-density lipoprotein (HDL), triglycerides, and albumin were measured on a monthly basis. RESULTS: All results are shown as mean SE. Total cholesterol values (in mg/ dL) were for group (A) 186 +/- 4, for group (B) 205 +/- 3, for group (C) 200 +/- 3, and for group (D) 203 +/- 4 [p NS between (C) and (D), p<.05 for all other comparisons]. Triglycerides values (in mg/dL) were for group (A) 171 +/- 9, for group (B) 199 +/- 6, for group (C) 190 +/- 6, and for group (D) 191 +/- 9 (p NS for all comparisons). HDL values (in mg/dL) were for group (A) 43.8 +/- 1, for group (B) 35.8 +/- 1, for group (C) 38.3 +/- 0.7, and for group (D) 37.2 +/- 0.7 mg/dL [p NS between (C) and (D), p<.001 for all other comparisons]. Low-density lipoprotein values (in mg/dL) were for group (A) 107.6 +/- 4.4, for group (B) 149.3 +/- 2.5, for group (C) 131.2 +/- 2.9, and for group (D) 126.8 +/- 4.1 [p NS between (C) and (D), p<.001 for all other comparisons]. Atherogenic index values, calculated as [triglycerides/HDL] ratio, were for group (A) 4.6 +/- 0.04 , for group (B) 6.2 +/- 0.04, for group (C) 4.9 +/- 0.03, and for group (D) 5.9 +/- 0.03 [p NS between (C) and (D), p<.004 for all other comparisons]. CONCLUSION: In nondiabetic hemodialysis patients, lipid profile abnormalities often accompany high levels of iPTH. The decrease in iPTH and/or the administration of CCB are accompanied by significant improvements in the main lipid profiles, including the atherogenic index.

Aged↗
PubMed1999

1,4-Dihydropyridine calcium channel blockers inhibit plasma and LDL oxidation and formation of oxidation-specific epitopes in the arterial wall and prolong survival in stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: Calcium-channel blockers (CCBs) reduce systolic blood pressure and stroke-related mortality in stroke-prone spontaneously hypertensive rats (SPSHR). Brain ischemia is associated with loss of intracellular antioxidants. Increased formation of oxygen radicals and oxidation of LDL may enhance arterial vasoconstriction by various mechanisms. CCBs that also exert antioxidative properties in vitro may therefore be particularly useful. To investigate such antioxidant effects in vivo, we determined several parameters of LDL oxidation in SPSHR treated with two 1,4-dihydropyridine-type (1,4-DHP) CCBs of different lipophilic properties and compared them with antioxidant-treated and untreated controls. We also tested whether these drugs decrease the formation of oxidation-specific epitopes in arteries. METHODS: Five groups of 9 to 14 SPSHR each (aged 8 weeks) were treated with 80 mg/kg body wt per day nifedipine, 1 mg or 0.3 mg/kg body wt per day lacidipine, vitamin E (100 IU/d), or carrier for 5 weeks. A group of Wistar-Kyoto rats was used as normotensive control. Plasma samples were taken, and LDL was isolated by ultracentrifugation. Then LDL was exposed to oxygen radicals generated by xanthine/xanthine oxidase reaction (2 mmol/L xanthine+100 mU/mL xanthine oxidase), and several parameters of oxidation were determined. The presence of native apolipoprotein B and oxidation-specific epitopes in the carotid and middle cerebral arteries was determined immunocytochemically. RESULTS: 1,4-DHP CCBs completely prevented mortality. Normotensive Wistar-Kyoto rats showed less oxidation than control SPSHR. Plasma lipoperoxide levels were 0.87+/-0.27 micromol/L in control SPSHR, 0.69+/-0.19 and 0.63+/-0.20 micromol/L in the groups treated with 0.3 and 1 mg lacidipine, respectively, and 0.68+/-0.23 micromol/L in nifedipine-treated animals (P<0.05 versus control SPSHR for all values). Both CCBs significantly decreased formation of conjugated dienes and prolonged the lag time in LDL exposed to oxygen radicals. Similarly, lipoperoxides and malondialdehyde were significantly reduced (P<0.05). Reduced relative electrophoretic mobility and increased trinitrobenzenesulfonic acid reactivity of LDL from treated rats (P<0.01) also indicated that fewer lysine residues of apolipoprotein B were oxidatively modified in the presence of 1,4-DHP CCBs. Finally, these drugs reduced the intimal presence of apolipoprotein B and oxidized LDL (oxidation-specific epitopes) in carotid and middle cerebral arteries. CONCLUSIONS: In the SPSHR model, 1,4-DHP CCBs reduce plasma and LDL oxidation and formation of oxidation-specific epitopes and prolong survival independently of blood pressure modifications. Our results support the concept that the in vivo protective effect of these drugs on cerebral ischemia and stroke may in part result from inhibition of oxidative processes.

Animals↗
PubMed1997

Nifedipine, an L-type calcium channel blocker, restores the hypnotic response in rats made tolerant to the alpha-2 adrenergic agonist dexmedetomidine.

Rats were made tolerant to the hypnotic effects of the alpha-2 adrenergic agonist dexmedetomidine by a 7- or 14-day continuous systemic administration of the same, and the ability of nifedipine to reverse dexmedetomidine tolerance was assessed. Acute administration of nifedipine (10 mg/kg i.p.) restored the hypnotic response to dexmedetomidine in the alpha-2 tolerant rats. Concurrent administration of nifedipine during induction of tolerance, either partially (continuous administration 10 mg/kg/day delivered by minipumps) or completely (twice daily injections, 20 mg/kg s.c.) restored hypnotic responsiveness to control levels. Induction of tolerance reduced the affinity of [3H]PN200-110 for the L-type calcium channel. Chronically administered nifedipine treatment (20 mg/kg s.c. twice daily), at doses that partially restored the behavioral response to normal, did not change ligand binding affinity of [3H]PN200-110. An increase in Bmax for [3H]PN200-110 was noted in the dexmedetomidine tolerant state which did not change with chronic nifedipine. In naive rats, the phosphodiesterase inhibitor rolipram (275 microg/kg i.p.), mimicked the state of tolerance, as it resulted in a decreased hypnotic response to dexmedetomidine. Nifedipine (10 mg/kg i.p.) also reversed the rolipram-induced attenuation of the hypnotic response to dexmedetomidine. These data implicate a role for the L-type calcium channel in the mechanism of the hypnotic response in alpha-2 tolerant rats and suggest the involvement of the cAMP pathway.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2006

Ziconotide--a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain--a short review.

Worldwide a large number of patients suffer from severe chronic pain even after treatment with opioids following the 3-step analgesic ladder developed by the WHO. Intraspinal agents, including morphine, have been tried as a fourth step. However, approximately 20% of cases remain refractory. Ziconotide, an intrathecal analgesic with orphan drug status, is a novel alternative for the management of chronic intractable pain. Ziconotide is a synthetic peptide based on the toxin of the fish-hunting marine snail, Conus magus. It is the first therapeutic agent in a new pharmacological class of "topically" active analgesics that selectively target neuron-specific (N-type), voltage-gated calcium channels. Ziconotide produces potent analgesia by interruption of Ca-dependent primary afferent transmission of pain signals in the spinal cord. Ziconotide was significantly more effective than placebo in the treatment of chronic malignant (p < 0.001) and non-malignant pain (p < 0.001). In several clinical studies morphine dosages could be substituted by ziconotide. The drug has a lag-time for the onset and offset of analgesia and adverse effects. Initial doses should therefore be low (2.4 microg/day) and titrated slowly (increasing up to a maximum of 21.6 microg/day in increases of 2.4 microg/day no more than twice weekly). The gradual increase in dose helps to reduce the incidence and severity of adverse events which affect primarily the central nervous system (e.g. dizziness, nausea, confusion). Ziconotide maintains its analgesic efficacy over months and does not cause tolerance, dependence or respiratory depression. Following intrathecal infusion ziconotide is distributed within the cerebral spinal fluid (CSF) where its clearance (0.38 ml/min) corresponds to the rate of turnover of the CSF. Negligible amounts of ziconotide are present in the systemic circulation where it is rapidly degraded by proteolysis. In conclusion, ziconotide is a new and valuable alternative analgesic for the acute and long-term treatment of severe pain, especially in patients refractory to opioids.

Analgesics, Non-Narcotic↗
PubMed1994

Relationship between baseline blood pressure and blood pressure decrease after calcium channel blockers in conscious rats.

OBJECTIVE: To determine whether vasodilators produce a fall in mean blood pressure (MBP) that is directly proportional to baseline MBP. DESIGN: The effects on blood pressure of three calcium channel blockers, nitrendipine, nisoldipine and verapamil, were compared with sodium nitroprusside, a drug acting through a different mechanism. The drugs were infused in conscious, unrestrained rats and their effect on MBP was measured. SETTING: Primary experimental. ANIMALS: Animals were divided into three groups according to their baseline MBP: high (greater than 119 mmHg), moderate (91 to 119 mmHg) and normal (less than 91 mmHg). INTERVENTIONS: Five successive infusion rates for each drug were tested in each animal. MBP readings were taken at the end of each infusion period (usually 10 mins). MAIN RESULTS: At the maximal dose infused, nitrendipine (0.57 mg/kg.min) lowered MBP 13 +/- 6 mmHg in the low MBP rats, 51 +/- 4 mmHg in the rats with moderate MBP and 83 +/- 8 mmHg in the rats with high MBP (P < 0.05 within groups). Similar results (ie, the greater the baseline MBP, the greater the fall in MBP) were obtained with nisoldipine and verapamil. In the same groups, sodium nitroprusside (0.096 mg/kg.min) produced a fall of 52 +/- 3 mmHg, 56 +/- 5 mmHg and 54 +/- 13 mmHg, respectively (not significant). CONCLUSIONS: Nitrendipine, nisoldipine and verapamil behave as antihypertensives since their effect increased as a function of the initial MBP, while sodium nitroprusside showed no effect related to baseline MBP.

Animals↗
PubMed2005

Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N-type calcium channel blocker, in the formalin test in conscious rats.

The present study was undertaken to elucidate the antinociceptive effect of intrathecal administration of huwentoxin-I (HWTX-I), a N-type calcium channel blocker from the venom of the Chinese bird spider Ornithoctonus huwena (Wang) [=Selenocosmia huwena wang], by comparison with omega-Conotoxin-MVIIA (omega-CTX-MVIIA) and morphine hydrochloride in the formalin test in conscious rats. Similar to omega-CTX-MVIIA and morphine, intrathecal pre-treatment with HWTX-I resulted in suppression of nociceptive behavior in a dose-dependent manner. The ED50 values of HWTX-I and omega-CTX-MVIIA were 0.28 and 0.19 microg/kg, respectively. It was also found that, at lower doses (0.1 and 0.5 microg/kg), the antinociceptive effect of HWTX-I was identical to that of omega-CTX-MVIIA, while omega-CTX-MVIIA acted more remarkably than HWTX-I at higher dose (1.0 microg/kg). However, the antinociception induced by omega-CTX-MVIIA were companied with motor dysfunction, and these side-effects became more evident with the doses of omega-CTX-MVIIA increasing. In contrast, HWTX-I did not show these side-effects at the doses of 0.5-1.0 microg/kg. Compared with HWTX-I and omega-CTX-MVIIA, the analgesic effect of intrathecal morphine hydrochloride was initiated faster, but lasted for a shorter time (about 2-3 h at 1.0 microg/kg) than that of HWTX-I and omega-CTX-MVIIA (about 4- 5 h at 1.0 microg/kg). Therefore, the present results show that, like omega-CTX-MVIIA, the intrathecal administration of HWTX-I is effective in antinociception in the rat model of the formalin test.

Analgesics↗
PubMed1998

Calcium channel blockers for prevention of noise trauma in otologic surgery.

One hundred patients were tested prior to otologic ear surgery in a prospective, randomized, double-blind study to assess the perioperative efficiacy of a calcium channel blocker (diltiazem) in preventing acoustical trauma during middle ear surgery. The patients were randomly divided into a therapy group (diltiazem), and a control group (placebo). Bone conduction hearing thresholds were examined preoperatively and followed at 1 day and 3 months postoperatively. Frequency-dependent changes in postoperative bone conduction and the number of patients with various degrees of postoperative hearing loss in both groups were statistically analyzed. The results indicated only a small postoperative hearing loss after ear surgery in both groups. There was a tendency for better results in the therapy group but this was not found to be statistically significant. Despite favorable results in animal trials utilizing different kinds of noise with the prophylactic application of diltiazem, further studies in humans will be needed to determine the role of calcium antagonist drugs in the prophylaxis or treatment of acoustical trauma.

Adolescent↗
PubMed1989

Calcium channel blocker reverses anticholinesterase-induced myopathy.

Inhibition of the enzyme, acetylcholinesterase (AChE), at the neuromuscular junction by pyridostigmine (PYR) results in breakdown of the postjunctional folds and dissolution of the Z-discs. It is hypothesized that excess activation of the acetylcholine (ACh) receptors by unhydrolyzed ACh results in a large influx of calcium ions. This could possibly lead to the activation of calcium-dependent proteases, resulting in the observed myopathy. Pretreatment with the calcium channel blocker, diltiazem, followed by administration of both PYR and the calcium blocker resulted in a significant reduction in the extent of muscle damage due to PYR alone. In order to ascertain whether the calcium blocker could reverse the myopathy previously induced by PYR, the AChE inhibitor was administered first, resulting in significant muscle damage, followed the next day by diltiazem. After 7 days of diltiazem treatment, with continued administration of PYR, the calcium blocker significantly reduced the myopathy at the neuromuscular junction. The results are discussed in terms of possible clinical application of diltiazem in neuromuscular diseases (i.e. muscular dystrophy).

Animals↗