Disease relevance of Emopamil

• The phenylalkylamine emopamil prevents brain damage due to experimental cerebral ischemia [1].
• The effects of the calcium entry blocker emopamil on physiological variables, local cerebral blood flow (LCBF) and on hippocampal cell damage were evaluated after 10 min of forebrain ischemia in the rat [2].
• The authors sought to determine whether amiloride or emopamil could reduce intracranial pressure in experimental brain edema of the rat [3].
• Effect of emopamil on cerebrocortical microcirculation during hypoxia and reactive hyperemia and on [K+]e, pH, pO2 changes during and after N2 anoxia [4].

High impact information on Emopamil

• We recently characterized (Moebius, F. F., Burrows, G. G., Striessnig, J., and Glossmann H. (1993) Mol. Pharmacol. 43, 139-144) and purified (Moebius, F. F., Hanner, M., Knaus, H. G., Weber, F., Striessnig, J., and Glossmann, H. (1994) J. Biol. Chem. 269, 29314-29320) a binding protein for the phenylalkylamine Ca2+ antagonist emopamil [5].
• The purified protein retained its high affinity for the antiischemic drugs emopamil (Kd = 4 nM), opipramol (IC50 = 15 nM), trifluoperazine (IC50 = 2 nM), and for Zn2+ (IC50 = 2 microM) [6].
• Using [N-methyl-3H]LU49888 as a photoaffinity probe we now provide evidence that the cation-sensitive emopamil binding site is localized on a 22-kDa polypeptide in guinea pig liver, kidney, lung, and adrenal gland [1].
• Effects of calcium entry blocker emopamil on postischemic energy metabolism of the isolated perfused rat brain [7].
• After 30 min of postischemic reperfusion, cortical levels of lactate were lower in emopamil-treated brains compared to controls at both constant pressure and constant volume perfusion [7].

Biological context of Emopamil

• Nimodipine and emopamil increased the blood glucose level and lowered preischemic blood pressure [8].
• Effect of amiloride and emopamil on intracranial pressure [3].

Anatomical context of Emopamil

• Preischemic application of emopamil [4 mg/kg racemate or 2 mg/kg (S)-emopamil; i.v.] caused increased in LCBF in cortical areas but did not alter blood flow in the hippocampus at 2 min of recirculation [2].
• According to these figures, emopamil is clearly superior to verapamil and gallopamil both with regard to cerebral availability and blood-brain barrier permeability [9].

Associations of Emopamil with other chemical compounds

• 4. The evoked increase of intracellular calcium in cortical neurones was inhibited with the following rank order of potency (IC50 value, microM): emopamil (3.6) > verapamil (17) > emopamil quaternary derivative (38) > verapamil quaternary derivative (200) [10].
• Pharmacologically-but not structurally-the sigma 1-site is also related to the emopamil binding protein, the mammalian sterol C8-C7 isomerase [11].
• Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase [12].
• The results suggest that the drug efficacy necessary to accelerate the restitution of postischemic energy metabolism is in the order of noremopamil greater than emopamil greater than gallopamil [13].
• In contrast to the DHP drugs, verapamil and (-)emopamil (which act at the phenylalkylamine binding sites), diltiazem and clentiazem (benzothiazepine binding sites), and the non-selective drug, flunarizine, were inactive in the tail suspension test [14].

Gene context of Emopamil

• 1. Verapamil and emopamil are structurally related phenylalkylamine calcium channel/5-HT2 receptor antagonists that differ in their anti-ischaemic properties in experimental studies [10].
• Analysis of the sigma(1) protein sequence confirmed homologies with the ERG2/emopamil binding protein family but also with the steroidogenic enzymes isopentenyl diphosphate isomerase and 17beta-estradiol dehydrogenase [15].

Analytical, diagnostic and therapeutic context of Emopamil

• When brains were perfused at constant flow rate, however, emopamil exhibited no effect on brain energy metabolism in the early reperfusion period [7].
• Global cerebral perfusion rate was increased by emopamil throughout the perfusion period and, accordingly, in brains perfused at a constant flow rate, perfusion pressure was reduced by the drug [7].
• The effects of emopamil on postischemic energy metabolism and electroencephalographic (EEG) recovery were investigated in the isolated rat brain perfused at either constant pressure or, alternatively, at constant flow rate [7].
• The protective effect of (-) Emopamil on renal function following warm and cold ischemia [16].

References