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At least 19 recordsLinked to original sources

PubMed1988

Basic mechanisms underlying prenylamine-induced 'torsade de pointes': differences between prenylamine and fendiline due to basic actions of the isomers.

The calcium antagonists prenylamine and fendiline both bind with rather low affinity to the dihydropyridine (nifedipine) binding site. As calmodulin (CaM) antagonists, they both inhibit CaM-dependent enzymes and relax smooth muscle preparation in nearly the same concentration range. If compared with other calcium antagonists, their action on smooth muscle develops rather slowly and cannot be inhibited by the calcium agonist Bay k 8644. In contrast, basic pharmacology reveals major differences of the actions of prenylamine and fendiline in heart muscle, indicating that, after all, the change in structure close to the asymmetric carbon strongly influences the molecular action of the compounds and their respective isomers. The negative inotropic effect of racemic prenylamine is rather independent of stimulation rate, whereas fendiline preferably depresses contraction at high rate stimulation. The negative inotropic potencies are determined by the (-)-isomers, but only in the case of prenylamine the isomeric ratio of 6 reveals a considerable stereoselectivity of action. In low concentrations and preferably at low rate stimulation, (+)-prenylamine exerts a strong positive inotropic effect. At low rate stimulation, total duration of transmembrane action potential is prolonged by (+/-)- and (+)-prenylamine, but discretely shortened by (+/-)- and (+)-fendiline. At high rate stimulation, it is shortened by (+/-)- and (-)-prenylamine, but prolonged (only) at the very final repolarization level by (+/-)- and (-)-fendiline. The positive inotropic action of prenylamine and the prolongation of action potential at low stimulation rate can be interpreted as a calcium agonistic side-effect due to the action of the (+)-isomer. It seems possible that, under the condition of low heart rate, prenylamine (as reported for the calcium agonist Bay k 8644) increases the potential-dependent transmembrane calcium current. In addition, it is argued that during the long-lasting action potential, a reactivation of the calcium current induces early after-depolarizations. These effects are postulated to represent the main mechanisms triggering torsade de pointes during therapy with prenylamine. Though fendiline, from a chemical point of view, rather resembles prenylamine, its pharmacological profile is different. In particular, in regard to electrophysiology, torsade de pointes are not expected to be induced by fendiline.

Animals↗

PubMed2002

Prenylamine block of Nav1.5 channel is mediated via a receptor distinct from that of local anesthetics.

We have shown previously that prenylamine, a calcium channel blocker, has potent local anesthetic activity in vivo and in vitro. We now characterize the tonic and use-dependent block of prenylamine on wild-type human cardiac voltage-gated sodium channels (hNav1.5) transiently expressed in human embryonic kidney 293t cells under whole-cell voltage-clamp condition. We also determine whether prenylamine and local anesthetics interact with a common binding site on the Nav1.5 channel by analyzing prenylamine block on mutant hNav1.5 channels that have substitution mutations in amino acids at the putative local anesthetic binding sites. Prenylamine exhibits tonic block at both hyperpolarizing and depolarizing potentials on hNav1.5 channels with 50% inhibitory concentrations of 9.67 +/- 0.25 microM and 0.72 +/- 0.02 microM, respectively. Substitutions of the amino acids at the putative local anesthetic binding site (i.e., F1760, N1765, Y1767, and N406) with lysine had much lesser effects on prenylamine block of the mutant hNav1.5 channels compared with local anesthetic block. The affinity of prenylamine was reduced at most by 5.8-fold, whereas that of bupivacaine, a known local anesthetic, was reduced by as much as 68-fold compared with wild-type by the mutations at the local anesthetic receptor site. Furthermore, equilibrium results between prenylamine-bupivacaine mixtures suggest two independent receptors. 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.

Anesthetics, Local↗

PubMed2001

Local anesthetic properties of prenylamine.

BACKGROUND: Local anesthetics that produce analgesia of long duration with minimal impairment of autonomic functions are highly desirable for pain management in the clinic. Prenylamine is a known calcium channel blocker, but its local anesthetic blocking effects on voltage-gated sodium channels have not been studied thus far. METHODS: The authors characterized the tonic and use-dependent prenylamine block of native Na(+) channels in cultured rat neuronal GH3 cells during whole cell voltage clamp conditions and the local anesthetic effect of prenylamine by neurologic evaluation of sensory and motor functions of sciatic nerve during neural block in rats. RESULTS: Prenylamine elicits both use-dependent block of Na(+) channels during repetitive pulses (3 microm prenylamine produced 50% block at 5 Hz) and tonic block for both resting and inactivated Na(+) channels. The 50% inhibitory concentration for prenylamine was 27.6 +/- 1.3 microm for resting channels and 0.75 +/- 0.02 microm for inactivated channels. 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. Rats injected with 15.4 mm bupivacaine, a known local anesthetic currently used for pain management, had a significantly shorter duration of blockade (< 2 h) compared with rats injected with prenylamine. CONCLUSIONS: The data presented here demonstrate that prenylamine possesses local anesthetic properties in vitro and elicits prolonged local anesthesia in vivo.

Anesthetics, Local↗

PubMed1977

Prenylamine-induced contracture of frog skeletal muscle.

1. Experiments were performed to determine the influence of prenylamine on excitation-contraction coupling in frog sartorius muscle. 2. Prenylamine (0.2-1.0 mM) produced a biphasic contracture in skeletal muscle characterized by an initial phasic and subsequent tonic contracture. 3. Neither dantrolene nor procaine blocked the prenylamine-induced contracture. Pretreatment with 100 mM K+ blocked the phasic but not the tonic component of the prenylamine contracture. 4. Prenylamine produced a sustained increase in 45Ca efflux at all concentrations that produce contracture. These concentrations of prenylamine also depressed the action potential, muscle twitch and resting potential. 5. Low concentrations of prenylamine (0.05 mM) which produced neither contracture, 45Ca efflux nor 45Ca influx, depressed the action potential, muscle twitch and K+ contracture. 6. The results suggest that prenylamine not only alters calcium mobility but also membrane permeability to other ions.

Action Potentials↗

PubMed1978

Effect of phentolamine, alprenolol and prenylamine on maximum rate of rise of action potential in guinea-pig papillary muscles.

Effects of phentolamine (13.3, 26.5 and 53.0 micron), alprenolol (3.5, 7.0 and 17.5 micron) and prenylamine (2.4, 4.8 and 11.9 micron) on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with Tyrode's solution. 1. Phentolamine, alprenolol and prenylamine reduced the maximum rate of rise of action potential (.Vmax) dose-dependently. Higher concentrations of phentolamine and prenylamine caused a loss of plateau in a majority of the preparations. Resting potential was not altered by any of the drugs. Readmittance of drug-free Tyrode's solution reversed these changes induced by 13.3 micron of phentolamine and all conconcentrations of alprenolol almost completely but those induced by higher concentrations of phentolamine and all concentrations of prenylamine only slightly. 2. .Vmax at steady state was increased with decreasing driving frequencies (0.5 and 0.25 Hz) and was decreased with increasing ones (2--5 Hz) in comparison with that at 1 Hz. Such changes were all exaggerated by the above drugs, particularly by prenylamine. 3. Prenylamine and, to a lesser degree, phentolamine and alprenolol delayed dose-dependently the recovery process of .Vmax in premature responses. 4. .Vmax in the first response after interruption of stimulation recovered toward the predrug value in the presence of the above three drugs. The time constants of recovery process ranged between 10.5 and 15.0s for phentolamine, between 4.5 and 15.5s for alprenolol. The time constant of the main component was estimated to be approximately 2s for the recovery process with prenylamine. 5. On the basis of the model recently proposed by Hondeghem and Katzung (1977), it is suggested that the drug molecules associate with the open sodium channels and dissociated slowly from the closed channels and that the inactivation parameter in the drug-associated channels is shifted in the hyperpolarizing direction.

Action Potentials↗

PubMed1982

Long-term prenylamine therapy: effects on responses to myocardial ischaemia in the isolated rat heart.

The effects of long-term administration of prenylamine gluconate were studied to define changes induced by chronic treatment that may alter the responses of the myocardium to ischaemic stress. Prenylamine gluconate was administered orally to rats (10 mg or 100 mg/kg per day) for 2 weeks. At the end of this period, hearts were excised for perfusion studies. In comparison with gluconate-treated controls, hearts from the group treated with the lower dose of prenylamine showed a significant reduction in basal cardiac function that was not apparent in the group treated with the higher dose of prenylamine. After a period (35 min) of ischaemia stress (reduced flow), a reduction in enzyme leakage and an increase in post-ischaemic functional recovery were observed in hearts from animals treated with the lower dose of prenylamine. In contrast, hearts from the group treated with the higher dose showed no significant improvement. However, chronic prenylamine therapy was shown to reduce in a dose-dependent manner the incidence of post-ischaemic arrhythmias. Thus, although the antiarrhythmic efficacy of long-term treatment with this agent appears to be proportional to the dosage, the ability of prenylamine to reduce ischaemic damage and promote functional recovery does not show a linear relationship with the drug dose.

Adenosine Triphosphate↗

PubMedDate not supplied

The role of prenylamine in the prevention of adriamycin-induced cardiotoxicity. A review of experimental and clinical findings.

Experimental and clinical trials to determine the potential of prenylamine in the prevention of adriamycin-related cardiotoxicity are reviewed. In mice given 4 mg/kg body weight adriamycin, the incidence of myocardial damage after 19 days' treatment was lower than in those given adriamycin and placebo. Rabbits were given adriamycin (total dose 10.8 mg/kg body weight), adriamycin plus prenylamine (1.5 mg/kg body weight), and adriamycin plus vitamins A (250 IU) and E (40 mg) for 9-11 weeks. Adriamycin-induced electrocardiogram changes were observed to a lesser extent in animals also receiving prenylamine. Heart homogenates from adriamycin-treated animals showed enhanced hydroperoxide-initiated chemiluminescence which was not affected by the simultaneous administration of prenylamine. The extent of adriamycin-induced myocytolysis and the degree of alterations observed on electron microscopy were markedly reduced by prenylamine. 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. In those given adriamycin plus placebo, two patients developed congestive cardiopathy and another showed severe supraventricular arrhythmias together with hypotension and dyspnoea. The mechanisms of adriamycin-related cardiotoxicity, the effects of prenylamine and the benefit from combined treatment are discussed.

Aged↗

PubMed1992

A gas chromatographic/mass spectrometric assay for prenylamine suitable for pharmacokinetic studies of the racemate and the enantiomers.

A sensitive assay for prenylamine and dideuteroprenylamine (racemic or pseudo-racemate) has been developed and used in human pharmacokinetic studies. Plasma levels of prenylamine could be measured up to 50 h after a single oral therapeutic dose. The extracted drug was derivatized with pentafluoropropionic anhydride in acetonitrile. The dried samples were reconstituted in decane; an aliquot was injected into a fused-silica capillary in a cooled on-column injector. The base peaks in the electron impact mass spectra of the compounds--derived by loss of a benzyl radical--at m/z 384, 386 and 390 were measured for prenylamine, (D2)-prenylamine and the internal standard hexahydroprenylamine, respectively. The sensitivity of this assay--limit of detection 0.2 ng ml-1 plasma with a signal-to-noise ratio of 5:1--allowed measurement of the kinetics of the racemate and of both stereoisomers for the first time. In man, the (+)-isomer was eliminated considerably faster than the (-)-prenylamine; the area under the plasma concentration time curve (AUC) of the (+)-isomer was only about 1/4 of the AUC of (-)-prenylamine.

Biological Availability↗

PubMedDate not supplied

Effects of prenylamine on transmembrane action potentials as related to the change in external potassium concentrations in guinea pig papillary muscle.

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. Prenylamine reduced Vmax at 1 Hz increasingly as the external potassium, [K]o, was increased from 2.7 to 10 mM. The reduction was also increased as the driving rate was increased from 0.25 to 5 Hz. The rate-dependent depression was less in 2.7 and 8.1 mM with 7.2 mM [Ca]o and more in 5.4 and 8.1 mM [K]o with 1.8 mM [Ca]o. Prenylamine produced a marked delay in the recovery of Vmax in premature responses inserted between constant driving stimuli at 0.25 Hz. The delay was also less in the former two, and more in the latter two media. Thus the effects of prenylamine on Vmax were more rate dependent and less [K]o-dependent than those of 36.9 microM lidocaine. At the diastolic interval of 100 ms, prenylamine depressed the overshoot, action potential duration at 0 mV level (APDo) and Vmax in premature responses more markedly than did 36.9 microM lidocaine, the differences of the effects being more significant for the first two. The results are interpreted as representing the calcium-antagonistic property of prenylamine of which lidocaine appears to be devoid.

Action Potentials↗

PubMed1984

The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion-induced arrhythmias in anaesthetized rats.

In male rats, anaesthetized with pentobarbitone, ligation of the main left coronary artery causes an early phase of ventricular arrhythmias which last about 30 min. In approximately 60% of control animals, ventricular fibrillation occurs but since spontaneous reversion to sinus rhythm may occur, mortality is of the order of 30%. When administered intravenously 15 min prior to ligation, verapamil (0.01 and 0.05 mg kg-1), prenylamine (0.5 mg kg-1), flunarizine (0.1, 0.25, 0.5 and 1.0 mg kg-1) and cinnarizine (0.25, 0.5 and 1.0 mg kg-1) protected against these arrhythmias. Higher doses of verapamil (0.1 and 0.5 mg kg-1), prenylamine (5 mg kg-1) and flunarizine (2.5 mg kg-1) did not afford a similar protection and mortality was increased to or above control values. 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. Prior to ligation, a sustained fall in mean arterial blood pressure was observed only following the administration of the highest doses of prenylamine, flunarizine and cinnarizine. Heart rate was reduced by administration of only the highest dose of prenylamine. These studies show that although the four calcium antagonists studied, i.e. verapamil, prenylamine, flunarizine and cinnarizine do suppress ischaemia-induced arrhythmias, this protective effect may be limited to a narrow concentration range.

Anesthesia↗

PubMedDate not supplied

In vitro cardiac electrophysiological effects of prenylamine.

In order to get information on some of the effects of prenylamine (bradycardic effect, negative inotropic effect, triggering of "torsade de pointes"), we studied with intracellular microelectrodes its electrophysiological actions on guinea-pig sinus node and papillary muscle, on sheep Purkinje fibers and rabbit sino-atrial node isolated myocytes. Prenylamine (10(-6)-10(-5) M) reduced the firing rate of sinus node preparations. This effect was associated with a slowing of the rates of diastolic depolarization, of depolarization and of repolarization, and with a slight depolarization of the maximum diastolic potential. A dose-dependent decrease of the slope of the first 100 msec of the diastolic depolarization was observed. Prenylamine (10(-6) M) also reduced the amplitude of the pacemaker current (If) recorded using the patch-clamp technique from rabbit sino-atrial node cells. Prenylamine (3 x 10(-7)-3 x 10(-6) M) dose-dependently reduced contractility of Purkinje fibers; the effect was associated with a lowering of the plateau, a decrease of the maximum rate of depolarization and a shortening of the action potential duration. Prenylamine was also able to abolish early and delayed after-depolarizations which are two kinds of calcium-dependent electrical activities relevant for the genesis of triggered arrhythmias, such as "torsade de pointes". It is concluded that prenylamine, a nonselective calcium antagonist, presents an intriguing in vitro electrophysiological profile which makes any extrapolation to its in vivo pharmacology extremely complex.

Action Potentials↗

PubMed1990

Pharmacokinetics of prenylamine racemate and enantiomers in man.

Pharmacokinetics of racemic prenylamine were investigated in 6 healthy volunteers. Plasma levels were determined by gas chromatography/mass spectrometry. Concentration-time profiles were analyzed both by compartment-dependent and compartment-independent pharmacokinetic models. Terminal elimination half-life was 14.1 h (SD: 6.9 h). The apparent total clearance was 5.8 l/min. Mean residence time of racemic prenylamine was found to be 14.7 h (SD: 3.8 h). The relative bioavailability of prenylamine (Segontin 100) was 82.2% (SD: 9.9%) determined in six healthy volunteers. The volunteers received simultaneously the film tablet and 100 mg racemic dideuteroprenylamine as an aqueous solution of the lactate. This procedure is known to exclude intraindividual changes in absorption, first-pass metabolism or volume of distribution that might occur on sequential administration. The absolute bioavailability was estimated to be in the order of 15%. In a pilot study the pharmacokinetics of the enantiomers were investigated in 2 healthy volunteers. S-(+)-prenylamine was eliminated considerably faster from plasma than R-(-)-prenylamine suggesting a stereoselective metabolism. The AUC of the (+)-enantiomer was 20% of that of the R-(-)-prenylamine.

Adult↗

PubMed1986

Amelioration of adriamycin-induced cardiotoxicity in rabbits by prenylamine and vitamins A and E.

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). 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). Heart homogenates from ADM-treated rabbits showed an increased hydroperoxide-initiated chemiluminescence (expressed as cpm/mg protein X 10(-3)) of 77 +/- 4 compared to control animals (52 +/- 1) (p less than 0.01). Prenylamine administration did not alter hydroperoxide-initiated chemiluminescence in ADM-treated rabbits, whereas treatment with a combination of vitamins A and E showed a significant decrease in hydroperoxide-initiated chemiluminescence in control (40 +/- 2) and ADM-treated rabbits (42 +/- 1). Microscopically, myocardial fibers had mild to severe hydropic vacuolization of sarcoplasm, which led to progressive myocytolysis. A total of 103 +/- 13 damaged fibers were detected over 700 counted fibers. Myocardial damage was lowered to 47 +/- 16 by administration of prenylamine and to 28 +/- 8 by administration of vitamins A and E. It is suggested that ADM leads to myocardial lipid peroxidation (ameliorated by vitamins A and E) with membrane damage and to an increase in calcium permeability, the latter being counteracted by prenylamine.

Animals↗

PubMed1993

Release of intracellular calcium by prenylamine in human ovarian tumour cells.

The effects of the calcium antagonist prenylamine on intracellular calcium concentration were studied in a human ovarian carcinoma cell line, OVCAR-3. Exposure of cells to 100 microM prenylamine resulted in nearly a 10-fold increase in cytosolic free calcium concentration ([Ca2+]i) as measured by Fura-2 fluorescence. In calcium-free medium, although the increase in [Ca2+]i caused by prenylamine was smaller, it was still substantial compared with the basal level. Efflux experiments with 45Ca showed that 100 microM prenylamine increased calcium efflux by 70% compared with control, indicating active extrusion of the elevated [Ca2+]i. The sluggish nature of calcium release and its independence from the pool activated by ionomycin suggest that the calcium was probably not released from endoplasmic reticulum. These results, although paradoxical, provide a new insight into the possible mechanism of action of prenylamine in causing cancer cell death.

Calcium↗

PubMed1975

Effects of prenylamine on cardiac membrane currents and contractility.

The influence of prenylamine on the electrical and mechanical activity of frog atrial muscle fibers has been studied under voltage clamp conditions. At a concentration of 10-4 M, prenylamine blocks the action potential without much affecting the resting potential. The drug depresses the peak transient sodium conductance with a dissociation constant of 1.7 times 10-5 M and on a one-to-one stoichiometric basis. The curve relating peak sodium conductance to membrane potential is slightly shifted in the direction of hyperpolarization. The time to peak sodium current and the rate of sodium inactivation are not significantly altered. 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. Recovery from sodium inactivation upon repolarization is distinctly slowed. The slow (secondary) inward current carried by calcium and/or sodium and the steady-state outward current are also depressed by prenylamine. The phasic (twitch-like) contraction related to the slow inward current is slightly decreased. The tonic (sustained) contraction associated with long-lasting depolarizations is increased and the time course of relaxation is retarded by prenylamine.

Action Potentials↗

PubMed1975

[Isotonic contraction and contracture of the isolated right rat ventricle. Effect of La3+, prenylamine, ATP, Mg2+ (author's transl)].

1. The isolated right rat ventricle was immersed in Tyrode solution (25) ml) and stimulated electrically at a frequency of 60/min. Changes in the amplitude of isotonic contractions and contractures were assessed. 2. Isotonic contractions were reduced (after Prenylamine, ATP, Mg), or suppressed (by LaCl3 = 10 mM). Contracture was caused by Prenylamine (4 mg/25 ml Tyrode solution or more). 3. Addition of 100 mM KCl (NaCl reduced equimolarily to 37 mM did not influence contracture in the presence of the investigated substances with the exception of MgCl2 = 10 to 15mM, where only the rate of development of potassium contracture was reduced. 4. After previous immersion of the tissue in the presence of LaCl3 - 10 mM and Prenylamine 1-4 mg/25 ml Tyrode solution the contracture developed after removal of NaCl (substitution by sucrose 270 mM), which, however, declined after addition of NaCl only when previously treated with Prenylamine and not when treated with La. 5. Addition of 100 mM KCl (naCl reduced to 37 mM) after previous immersion of the tissue in the presence of the investigated substances caused contracture the rate of rise of which was smaller after La than in controls: after the remaining substances it did not differ. 6. Reduction of the contracture after reduction of KCl from 100 to 5.6 mM developed only after previous immersion of the tissue in the presence of ATP and Mg and not after previous immersion in the presence of Prenylamine and La. 7. The results are compared with biochemical findings. They suggest a shift of contractile Ca in the heart.

Adenosine Triphosphate↗

PubMed1996

Effect of a prenylamine analog (MG8926) on spontaneous action potentials in isolated rabbit sinoatrial node.

Effects of verapamil, prenylamine and a prenylamine analog, MG8926 on the intracellular spontaneous action potentials recorded from the isolated rabbit sinoatrial (SA) node were studied. Verapamil (1 microM), a selective inhibitor for slow Ca2+ channels, prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential, the amplitude of action potential and the maximal diastolic potential, and usually arrested showing subthreshold fluctuation of the membrane potential within several ten min. Prenylamine (10 microM), a nonselective inhibitor for slow Ca2+ channels, tended to prolong the cycle length to decrease the diastolic depolarization, the rate of rise of action potential, the amplitude of action potential. However, these changes were statistically insignificant. Prenylamine at the concentration of 10 microM had no effect on the maximal diastolic potential. MG8926 (10 microM) prolonged the cycle length, decreased the rate of diastolic depolarization, the rate of rise of action potential and tended to decrease the amplitude of action potential. MG8926 at the concentration of 10 microM had almost no effect on the maximal diastolic potential. The present findings may indicate that replacement of phenyl residue of prenylamine by cyclohexyl residue increases the inhibitory action on the slow Ca2+ channels in rabbit SA node.

Action Potentials↗

PubMed1990

Single- and multiple-dose pharmacokinetics of R-(-)-and S-(+)-prenylamine in man.

The pharmacokinetics of S-(+)- and R-(-)-prenylamine was studied in eight healthy volunteers given single and repeated oral doses of the racemic drug. Distinct differences in various pharmacokinetic parameters were found between the S- and R-enantiomer. The maximum plasma concentrations and AUCs of the R-enantiomer exceeded those of the S-enantiomer five-fold; the apparent oral clearance of the S-form was five-times and the renal clearance three-times higher than of the R-form. Acid catalyzed hydrolysis of urine samples released more S-prenylamine, indicating stereoselective glucuronidation of unchanged prenylamine. Plasma protein binding also differed between the two enantiomers, generally with a higher unbound fraction of the S-form, whereas analysis of the bound fractions showed that prenylamine was bound to different plasma proteins with inverse stereoselectivity.

Adult↗