Disease relevance of PRENYLAMINE

• Torsade de pointes with prenylamine: do we still need the drug [1]?
• 4. Prenylamine produced a sustained increase in 45Ca efflux at all concentrations that produce contracture [2].
• Protective effect of prenylamine against vulnerability to ventricular fibrillation in the normal and ischemic canine myocardium [3].
• Death was due in prenylamine-treated rats to atrioventricular block leading to asystole whereas in those administered verapamil or flunarizine it was a consequence of persistent ventricular fibrillation [4].
• The galectin-3-induced effect is insensitive to voltage-gated Ca2+ channel antagonists such as prenylamine, nifedipine and diltiazem and to pertussis toxin but is inhibited by cholera toxin [5].

High impact information on PRENYLAMINE

• Thus, the data demonstrate that prenylamine has both tonic and use-dependent block of hNav1.5 channels similar to that of local anesthetics, but the location of the prenylamine binding site on hNav1.5 differs from that of the local anesthetic binding site [6].
• Prenylamine block of Nav1.5 channel is mediated via a receptor distinct from that of local anesthetics [6].
• On the other hand, binding of the CaM antagonist drugs prenylamine and calmidazolium or the potent peptide antagonist melittin did not alter MIANS fluorescence [7].
• The 50% inhibitory concentration for prenylamine was 27.6 +/- 1.3 microm for resting channels and 0.75 +/- 0.02 microm for inactivated channels [8].
• Furthermore, in vivo data show that 10 mm prenylamine produced a complete sciatic nerve block of motor function, proprioceptive responses, and nociceptive responses that lasted approximately 27, 34, and 24 h, respectively [8].

Chemical compound and disease context of PRENYLAMINE

• Torsade de pointes due to prenylamine controlled by lignocaine [9].
• 3. Neither dantrolene nor procaine blocked the prenylamine-induced contracture [2].
• The cardioprotective potentials of prenylamine (a calcium antagonist) and of a combination of vitamins A and E (a singlet oxygen quencher and a free radical scavenger, respectively) were evaluated in rabbits given chronically large doses of Adriamycin (ADM) (10.8 mg/kg body weight for 9 to 11 weeks) [10].
• The MTX-induced hemolysis was little affected by L-type Ca(2+) channel blockers (diltiazem, nifedipine, verapamil) but was strongly inhibited by calmodulin blockers (prenylamine and chlorpromazine) or a phospholipase A2 inhibitor (quinacrine) [11].
• Effects of prenylamine and AQ-A 39 on reentrant ventricular arrhythmias induced during the late myocardial infarction period in conscious dogs [12].

Biological context of PRENYLAMINE

• In concentrations of 10-50 microM, prenylamine significantly (P less than 0.01) shortened action potentials, and significantly (P less than 0.001) reduced the inward calcium current by 29% to 76% (n = 7) [13].
• Heart rate was reduced by administration of only the highest dose of prenylamine [4].
• With 2 times 10-5 M prenylamine, the steady-state sodium inactivation curve is shifted by 5 mV to more negative membrane potentials but the decreased availability of the sodium system at the resting level is not sufficient to account for the reduction of sodium current [14].
• We have compared the cardioprotective agents prenylamine and glyceryl trinitrate (GTN) with respect to their effects on the bioenergetics of catecholamine storage vesicles [15].
• 1 The antidysrhythmic, haemodynamic and metabolic effects of a new prospective antianginal and antidysrhythmic agent, N-(3-3-dipenylpropyl)-alpha-methyl-beta-cyclohexylethylamine hydrochloride (MG 8926), have been compared with the chemically related substance, prenylamine, in anaesthetized greyhounds and guinea-pigs [16].

Anatomical context of PRENYLAMINE

• The effects of prenylamine on single ventricular myocytes of guinea-pig [13].
• Prenylamine-induced contracture of frog skeletal muscle [2].
• The influence of prenylamine on the electrical and mechanical activity of frog atrial muscle fibers has been studied under voltage clamp conditions [14].
• Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), chlorpromazine, prenylamine and N2-dansyl-L-arginine-4-t-butylpiperidine amide on vascular smooth muscle contraction were compared by using helically cut strips of rabbit aorta [17].
• We examined the effects of four Ca2+ antagonists that possess the ability to bind to calmodulin-felodipine, nitrendipine, prenylamine, and verapamil--as well as the effect of the calmodulin antagonist trifluoperazine on Ca2+ uptake and Ca2+ + Mg2+/ATPase activity in canine cardiac sarcoplasmic reticulum [18].

Associations of PRENYLAMINE with other chemical compounds

• Rather, prenylamine simply displaces felodipine from its binding site on this fragment [19].
• However, in functional studies, contractile responses to endothelin (1 x 10(-8) M) in the endothelium-denuded aorta of the rat were potently reversed by nifedipine, verapamil, and prenylamine (-log IC50 values = 8.0 +/- 0.13, 7.2 +/- 0.09 and 6.6 +/- 0.08, n = 4-8, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)[20]
• IC50 values to inhibit cAMP (20 pmol/oocyte)-induced K+ currents were 126 microM for prenylamine and 129 microM for chlorpromazine [21].
• Antianginal drugs tested inhibited 3H-BTX-B binding in rat synaptosomes, arylalkylamine derivatives being the most potent: IC50 values were 27 nM for flunarizine, 32 nM for prenylamine, 79 nM for cinnarizine [22].
• 1. Phentolamine, alprenolol and prenylamine reduced the maximum rate of rise of action potential (.Vmax) dose-dependently [23].

Gene context of PRENYLAMINE

• Prenylamine also was a weak inhibitor, which was unexpected because of its CaM binding potency [24].
• The inhibitory effect of Ca2+/CaM was attenuated by the CaM antagonists W-7, prenylamine and CaM-kinase II fragment (290-309), but not by the calcineurin inhibitor FK506 [25].
• The hydrophobic calcium antagonists prenylamine and bepridil, however, interacted with [3H]diltiazem binding at concentrations up to 50 times lower than their calmodulin inhibiting concentrations [26].
• In a double-blind clinical trial with 26 oncological patients, no cardiomyopathy, arrhythmia or adverse reactions were observed in the group given adriamycin plus prenylamine [27].
• VUF 8929 (N-¿2-[bis(p-fluorophenyl)methoxy]ethyl¿-(2-phenyl)ethylamine maleate, CAS 140890-71-7) is a diphenylalkylamine derivative structurally related to prenylamine [28].

Analytical, diagnostic and therapeutic context of PRENYLAMINE

• CONCLUSIONS: The data presented here demonstrate that prenylamine possesses local anesthetic properties in vitro and elicits prolonged local anesthesia in vivo [8].
• Among ADM-treated rabbits, 8 of 10 showed post-treatment ECG changes; in rabbits treated with ADM and prenylamine, changes were found in a smaller number (5 of 10); and in animals treated with ADM and vitamins A and E, the incidence was only one in six (p less than 0.05) [10].
• We studied the effects of 4.8 muM prenylamine on transmembrane potentials in isolated guinea pig papillary muscles using a conventional microelectrode technique and compared them with those of 36.9 microM lidocaine [29].
• Prenylamine and the myocardial response to ischaemia and reperfusion: effects of acute and chronic treatment [30].
• Amphetamine concentrations in human urine following single-dose administration of the calcium antagonist prenylamine-studies using fluorescence polarization immunoassay (FPIA) and GC-MS [31].

References