Mephentermine hemisulfate monohydrate: an adrenergic agent.

The title molecule, a hydrated hemisulfate salt of ethyl(2-methyl-1-phenyl-2-propyl)ammonium, C11H18N+.0.5SO4(2-).H2O, consists of a phenethylamine skeleton in which the N atom is protonated. There are two molecules in the asymmetric unit, with the S atom of the SO4(2-) ion lying on a pseudo-twofold axis. The ethylamine side chain is in an extended conformation in both the symmetry-independent molecules. The distance of the N atom from the centre of the benzene ring is 5.1 A for molecule 1 and 5.3 A for molecule 2. The packing is stabilized by N-H...O and O-H...O hydrogen bonds.

Metabolism of mephentermine and its derivatives by the microsomal fraction from male Wistar rat livers.

1. The N-demethylation of mephentermine (MP), p-hydroxymephentermine (p-hydroxy-MP) and N-hydroxymephentermine (N-hydroxy-MP), to produce phentermine (Ph), p-hydroxyphentermine (p-hydroxy-Ph) and N-hydroxyphentermine (N-hydroxy-Ph), and the p-hydroxylation of MP and Ph, to produce p-hydroxy-MP and p-hydroxy-Ph, were examined using rat liver microsomal preparations containing NADPH. Microsomal reduction of N-hydroxy-Ph to Ph was also examined using various cofactors. In addition, enzymic system for the N-demethylation and p-hydroxylation were examined using various inhibitors. 2. N-Hydroxy-MP demethylation to N-hydroxy-Ph proceeded at a rate almost 10-fold faster than other reactions. MP demethylation to Ph, MP oxidation to P-hydroxy-MP, Ph oxidation to p-hydroxy-Ph proceeded at similar rates, whilst p-hydroxy-MP demethylation to p-hydroxy-Ph was catalysed at the slowest rate. Microsomal reduction of N-hydroxy-Ph to Ph required NADH, and the activity was similar to that of MP oxidation to p-hydroxy-MP. 3. N-Demethylation of MP, p-hydroxy-MP and N-hydroxy-MP were inhibited not only by inhibitors of cytochrome P450, but also by methimazole, an inhibitor of the FAD-monooxygenase system. p-Hydroxylations of MP and Ph were inhibited only by inhibitors of cytochrome P450.

The formation of metabolites of mephentermine by microsomal and cytosolic preparations of male Wistar rat livers.

1. Metabolites of mephentermine (MP), phentermine (Ph), p-hydroxy-MP, p-hydroxy-Ph, N-hydroxy-MP and N-hydroxy-Ph on incubation with rat liver microsomal and cytosolic preparations were identified by g.l.c. and g.l.c.-mass spectrometry. 2. Identification of the metabolites indicated the following new metabolic routes of MP: NADPH-dependent microsomal formation of p-hydroxy-MP from MP, of p-hydroxy-Ph from p-hydroxy-MP, and the NADH-dependent microsomal formation of Ph from N-hydroxy-Ph.

Metabolism of mephentermine in male guinea pigs and male mice.

1. Urinary metabolites of mephentermine (MP), after i.p. administration of MP to male Hartley guinea pigs and mice, were identified by g.l.c.-electron impact (EI) mass spectrometry. Excretion of urinary radioactivity, and metabolites of 3H-MP, after i.p. administration, were determined by preparative t.l.c.-liquid scintillation counting. 2. About 27% of the radioactivity administered was excreted in the 24 h urine of guinea pigs, and 36% dose was excreted in 5 days. In mice, about 47% of the radioactivity was excreted in the 24 h urine, and 52% in 5 days. 3. Excretion rates of metabolites detected in the 24 h urine of guinea pigs were phentermine (Ph, 7.8%), a conjugate of N-hydroxyphentermine (N-hydroxy-Ph, 3.6%), p-hydroxyphentermine (p-hydroxy-Ph, 1.0%) and its conjugate (2.9%), and other metabolites (conjugates of MP and Ph, N-hydroxymephentermine (N-hydroxy-MP) and its conjugate, p-hydroxymephentermine (p-hydroxy-MP) and its conjugate, and N-hydroxy-Ph; less than 1.0%). The rates of excretion for mice were Ph (11.7%), conjugates of p-hydroxy-MP (3.1%), Ph (2.7%) and p-hydroxy-Ph (1.6%), and N-hydroxy-Ph (1.2%) and other metabolites (conjugates of MP and N-hydroxy-Ph, N-hydroxy-MP and its conjugate, p-hydroxy-Ph, and p-hydroxy-MP; less than 1.0%). 4. These results indicate that MP administered to mice is metabolized mainly to Ph and p-hydroxy-MP by N-demethylation and p-hydroxylation of the parent compound, and in guinea pigs the primary metabolic reaction of MP is N-demethylation producing Ph.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation of urinary p-hydroxylated metabolites of mephentermine and phentermine in male Wistar rats.

1. p-Hydroxymephentermine (p-hydroxy-MP) and p-hydroxyphentermine (p-hydroxy-Ph) were isolated as hydrochlorides from urine of male Wistar rats repeatedly dosed with mephentermine (MP). In addition, p-hydroxy-Ph was isolated as the hydrochloride from urine of the rats dosed with phentermine (Ph). 2. These results substantiate previous indications that p-hydroxylation of MP and Ph was a primary metabolic reaction in the rat.