Verapamil reversal

Bellamy, W.T., Dalton, W.S., Kailey, J.M., Gleason, M.C., McCloskey, T.M., Dorr, R. T. and Alberts, D.S. (1988) Verapamil reversal of doxorubicin resistance in multidrug-resistant human myeloma... 

Verapamil reversed digoxin-induced splanchnic vasoconstriction in healthy men (243), but this has no direct effect on systemic hemodynamics. 

Chaube SK, Dubey PK, Mishra SK, Shrivastav TG. 2007. Verapamil reversibly inhibits spontaneous parthenogenetic activation in aged rat eggs cultured in vitro. Cloning... 

The multidrug resistance (mdr) reversing effect of the new phenothiazine complexes were tested on mouse T cell lymphoma cell lines. Trifluoperazine (TFP) was much more effective at the same concentration than verapamil. The efficacy of some metal coordination complexes [TFP-Cu(ll) and TFP-V(IV)] exceeded the action of TFP alone. Chlorpromazine (CPZ) or CPZ-Pt(ll) complex had the same or less effect than verapamil or promethazine (Pz) used as a control. 

G., Raschack, M., Cappelletto, B., Gigante, M., Boiocchi, M., Structure—activity relationship of verapamil analogs and reversal of multidrug resistance, Biochem. Pharmacol. 1995, 50, 1245-1255. 

Varian (see Catalog, SPE products) Focus Polar functionalized styrene-divinylbenzene polymer Reversed phase with strong hydrogen bond donor, acceptor, and dipolar character Fluoxetine, verapamil, olanzapine, tramadol, loratidine, and sumatriptane (81) verdanafil (82)... 

Lavie Y., Cao H.t., Volner A., Lucci A., Han T.Y., Geffen V., Giuhano A.E., and Cabot M.C., 1997, Agents that reverse multidmg resistance, tamoxifen, verapamil, and cyclosporin A, block gjycosphingolipid metabolism by inhibiting ceramide glycosylation in human cancer cells./. Biol. Chem. 272 1682-1687. 

Vincristine resistance has been studied in Chinese hamster ovary cell lines cells resistant to vincristine also are resistant to vinblastine and vindesine. Suggestions were made that, in cells with relatively low levels of drug resistance, at least two prominent mechanisms of resistance can occur (22). In the first instance, cellular resistance may be attributable to membrane alterations that are reversible, functionally, by treatment with verapamil. In the second, resistance has been postulated to be due to an altered sensitivity of tubulin to the effects of the drugs the primary basis for postulating an altered interaction with tubulin was that a subgroup of cells resistant to vincristine showed enhanced sensitivity to taxol, a drug that can stabilize microtubules. It should be emphasized that differential sensitivities of tubulins from different tumor cells to the effects of vincristine or vinblastine has been proposed as a basis for the susceptibilities of cells to the cytotoxic effects of such drugs (23). Differences have been described in the electrophoretic patterns for tubulins obtained from vin-... 

However, the reverse is not necessarily true all compounds that block the hERG channels do not prolong action potentials. Part of the reason lies in the fact that many compounds have a mixed effect on ion channels, particularly due to the blocking effect on both hERG and the L-type calcium channel [21], which is responsible for phase 2 of the cardiac action potential (Figure 16.1). Examples for such dual-blockers include bepridil, verapamil and mibefradil [22], all blocking hERG and L-type calcium channels at the therapeutic concentrations. However, only verapamil has nearly no cardiac liabilities. 

The concept of calcium antagonism as a specific mechanism of drug action was pioneered by Albrecht Fleckenstein and his colleagues, who observed that verapamil and subsequently other drugs of this class mimicked in reversible fashion the effects of Ca++ withdrawal on cardiac excitability. These drugs inhibited the Ca" + component of the ionic currents carried in the cardiac action potential. Because of this activity, these drugs are also referred to as slow channel blockers, calcium channel antagonists, and calcium entry blockers. 

Miller TP, Grogan TM, Dalton WS, et al P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high-dose verapamil. J Clin Oncol 9 17-24, 1991... 

Verapamil has been shown to block the P-glycoprotein responsible for the transport of many foreign drugs out of cancer (and other) cells (see Chapter 1) other calcium channel blockers appear to have a similar effect. This action is not stereospecific. Verapamil has been shown to partially reverse the resistance of cancer cells to many chemotherapeutic drugs in vitro. Some clinical results suggest similar effects in patients (see Chapter 54). Animal research suggests possible future roles of calcium blockers in the treatment of osteoporosis, fertility disorders and male contraception, immune modulation, and even schistosomiasis. 

Resistance to chloroquine is now very common among strains of P falciparum and uncommon but increasing for P vivax. In P falciparum, mutations in a putative transporter, PfCRT, have been correlated with resistance. Chloroquine resistance can be reversed by certain agents, including verapamil, desipramine, and chlorpheniramine, but the clinical value of resistance-reversing drugs is not established. 

Frazier, A. A., and K. K. Karukstis. 1997. Investigation of competitive binding between daunomycin and verapamil or genistein in AOT reverse micell dastracts of 213th ACS National Meeting, 262. 

Bebawy et al. [186] demonstrated that CPZ (9) and vinblastine inhibited each other s transport in a human lymphoblastic leukemia cell line (CCRF-CEM/VLBioo). CPZ (9) reversed resistance to vinblastine but not to fluores-cently labeled colchicine and it increased resistance to colchicine. Colchicine was supposed to be transported from the inner leaflet of the membrane and vinblastine from the outer leaflet. CPZ (9) was assumed to be located in the inner membrane leaflet where it interacts with anionic groups of phospholipids and it may inhibit vinblastine transport via allosteric interactions. The authors concluded that transport of P-gp substrates and its modulation by CPZ (9) (or verapamil (79)) are dependent on substrate localization inside the membrane. Contrary to CPZ (9) location in the inner leaflet of the membrane, other modulators and substrates of P-gp were proved to be rather localized within the interface region of the membrane. The location of seven P-gp substrates and two modulators within neutral phospholipid bilayers was examined by NMR spectroscopy by Siarheyeva et al. [129]. The substrates and the modulators of P-gp were found in the highest concentrations within the membrane interface region. The role of drug-lipid membrane interactions in MDR and its reversal was reviewed in detail elsewhere [53,187]. 

L. Miller and R. Bergeron, Analytical and preparative resolution of enantiomers of verapamil and norverapamil using a cellulose-based chiral stationary phase in the reversed-phase mode, J. Chromatogr., 648 36(1993)... 

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