scholarly journals Metabolism of [14C]methamphetamine in man, the guinea pig and the rat

1972 ◽  
Vol 129 (1) ◽  
pp. 11-22 ◽  
Author(s):  
J. Caldwell ◽  
L. G. Dring ◽  
R. T. Williams
Keyword(s):  
Guinea Pig ◽  
Benzoic Acid ◽  
Methyl Ketone ◽  
Species Differences ◽  
Human Subjects ◽  
Main Reaction ◽  
Unchanged Drug ◽  
Aromatic Hydroxylation ◽  
Dose Dependent ◽  
Acid Labile

1. The metabolites of (±)-2-methylamino-1-phenyl[1-14C]propane ([14C]methamphetamine) in urine were examined in man, rat and guinea pig. 2. In two male human subjects receiving the drug orally (20mg per person) about 90% of the14C was excreted in the urine in 4 days. The urine of the first day was examined for metabolites, and the main metabolites were the unchanged drug (22% of the dose) and 4-hydroxymethamphetamine (15%). Minor metabolites were hippuric acid, norephedrine, 4-hydroxyamphetamine, 4-hydroxynorephedrine and an acid-labile precursor of benzyl methyl ketone. 3. In the rat some 82% of the dose of14C (45mg/kg) was excreted in the urine and 2–3% in the faeces in 3–4 days. In 2 days the main metabolites in the urine were 4-hydroxymethamphetamine (31% of dose), 4-hydroxynorephedrine (16%) and unchanged drug (11%). Minor metabolites were amphetamine, 4-hydroxyamphetamine and benzoic acid. 4. The guinea pig was injected intraperitoneally with the drug at two doses, 10 and 45mg/kg. In both cases nearly 90% of the14C was excreted, mainly in the urine after the lower dose, but in the urine (69%) and faeces (18%) after the higher dose. The main metabolites in the guinea pig were benzoic acid and its conjugates. Minor metabolites were unchanged drug, amphetamine, norephedrine, an acid-labile precursor of benzyl methyl ketone and an unknown weakly acidic metabolite. The output of norephedrine was dose-dependent, being about 19% on the higher dose and about 1% on the lower dose. 5. Marked species differences in the metabolism of methamphetamine were observed. The main reaction in the rat was aromatic hydroxylation, in the guinea pig demethylation and deamination, whereas in man much of the drug, possibly one-half, was excreted unchanged.

scholarly journals The metabolic fate of amphetamine in man and other species

1970 ◽  
Vol 116 (3) ◽  
pp. 425-435 ◽  
Author(s):  
L. G. Dring ◽  
R. L. Smith ◽  
R. T. Williams
Keyword(s):  
Guinea Pig ◽  
Rhesus Monkey ◽  
Benzoic Acid ◽  
Acid Hydrolysis ◽  
Rhesus Monkeys ◽  
Methyl Ketone ◽  
Metabolic Fate ◽  
Unchanged Drug ◽  
Main Metabolite ◽  
Acid Labile

1. The fate of [14C]amphetamine in man, rhesus monkey, greyhound, rat, rabbit, mouse and guinea pig has been studied. 2. In three men receiving orally 5mg each (about 0.07mg/kg), about 90% of the 14C was excreted in the urine in 3–4 days. About 60–65% of the 14C was excreted in 1 day, 30% as unchanged drug, 21% as total benzoic acid and 3% as 4-hydroxyamphetamine. 3. In two rhesus monkeys (dose 0.66mg/kg), the metabolites excreted in 24h were similar to those in man except that there was little 4-hydroxyamphetamine. 4. In greyhounds receiving 5mg/kg intraperitoneally the metabolites were similar in amount to those in man. 5. Rabbits receiving 10mg/kg orally differed from all other species. They excreted little unchanged amphetamine (4% of dose) and 4-hydroxyamphetamine (6%). They excreted in 24h mainly benzoic acid (total 25%), an acid-labile precursor of 1-phenylpropan-2-one (benzyl methyl ketone) (22%) and conjugated 1-phenylpropan-2-ol (benzylmethylcarbinol) (7%). 6. Rats receiving 10mg/kg orally also differed from other species. The main metabolite (60% of dose) was conjugated 4-hydroxyamphetamine. Minor metabolites were amphetamine (13%), N-acetylamphetamine (2%), norephedrine (0.3%) and 4-hydroxynorephedrine (0.3%). 7. The guinea pig receiving 5mg/kg excreted only benzoic acid and its conjugates (62%) and amphetamine (22%). 8. The mouse receiving 10mg/kg excreted amphetamine (33%), 4-hydroxyamphetamine (14%) and benzoic acid and its conjugates (31%). 9. Experiments on the precursor of 1-phenylpropan-2-one occurring in rabbit urine suggest that it might be the enol sulphate of the ketone. A very small amount of the ketone (1–3%) was also found in human and greyhound urine after acid hydrolysis.

scholarly journals Species differences in the metabolism of sulphadimethoxine

1968 ◽  
Vol 109 (5) ◽  
pp. 851-856 ◽  
Author(s):  
J W Bridges ◽  
M. R. Kibby ◽  
S R Walker ◽  
R T Williams
Keyword(s):  
Guinea Pig ◽  
Species Differences ◽  
Glucuronic Acid ◽  
Acetyl Derivative ◽  
Unchanged Drug ◽  
Rat Urine ◽  
Monkey Liver ◽  
Liver Homogenates ◽  
Rat Bile ◽  
Do So

1. The fate of sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) was studied in man, rhesus monkey, dog, rat, guinea pig and rabbit. 2. About 20–46% of the dose (0·1g./kg.) of the drug is excreted in the urine in 24hr. in these species, except the rat, in which only 13% is excreted. 3. In man and the monkey sulphadimethoxine N1-glucuronide is the major metabolite in the urine. In the rabbit and guinea pig N4-acetylsulphadimethoxine is the main metabolite. In the dog the drug is excreted mainly unchanged. In the rat equal amounts of the unchanged drug and its N4-acetyl derivative are the main products. 4. Small amounts of sulphadimethoxine N4-glucuronide are found in the urine of all the species. Sulphadimethoxine N1-glucuronide occurs in small amounts in the urine of rat, dog and guinea pig; none is found in rabbit urine. 5. Sulphadimethoxine N4-sulphate was synthesized and found to occur in small amounts in rat urine. 6. Monkey liver homogenates fortified with UDP-glucuronic acid are able to synthesize sulphadimethoxine N1-glucuronide with the drug as substrate. Rat liver has also this ability to a slight extent, but rabbit liver is unable to do so. 7. Sulphadimethoxine N4-glucuronide is formed spontaneously when the drug is added to human urine. 8. The biliary excretion of the drug and its metabolites was examined in rats. The drug is excreted in rat bile mainly as the N1-glucuronide. The N1- and N4-glucuronides administered as such are extensively excreted in the bile by rats.

scholarly journals Biliary excretion in foreign compounds. Species difference in biliary excretion

1967 ◽  
Vol 105 (3) ◽  
pp. 1289-1293 ◽  
Author(s):  
M M Abou-el-Makarem ◽  
P Millburn ◽  
R L Smith ◽  
R T Williams
Keyword(s):  
Molecular Weight ◽  
Guinea Pig ◽  
Rhesus Monkey ◽  
Benzoic Acid ◽  
Biliary Excretion ◽  
Hippuric Acid ◽  
Species Differences ◽  
General Trend ◽  
Species Difference ◽  
Molecular Weights

1. The biliary excretion of injected [14C]aniline, [14C]benzoic acid, 4-amino-hippuric acid and 4-acetamidohippuric acid in six or eight species of animal (rat, dog, hen, cat, rabbit, guinea pig, rhesus monkey and sheep) was studied. 2. These compounds, with molecular weights in the range 93–236, are poorly excreted in the bile in all the species examined and, in effect, there is little significant species difference in the extent of their biliary excretion. 3. Compounds of higher molecular weight (355–495) were also studied, namely succinylsulphathiazole, [14C]stilboestrol glucuronide, sulphadimethoxine N1-glucuronide and phenolphthalein glucuronide. 4. With these compounds a clear species difference in the extent of biliary excretion was found, the rat, dog and hen being good excretors, the rabbit, guinea pig and monkey poor excretors, and the cat and sheep taking an intermediary position. 5. There was a general trend for biliary excretion to be higher in all species when the compounds were of higher molecular weight. 6. These results are discussed in their relation to species differences in drug metabolism.

scholarly journals Species differences in the metabolism of norephedrine in man, rabbit and rat

1973 ◽  
Vol 136 (3) ◽  
pp. 763-771 ◽  
Author(s):  
Joseph E. Sinsheimer ◽  
L. Graham Dring ◽  
R. Tecwyn Williams
Keyword(s):  
Hippuric Acid ◽  
Species Differences ◽  
Degradation Products ◽  
Human Subjects ◽  
Side Chain ◽  
Unchanged Drug ◽  
Main Metabolite

1. (±)-2-Amino-1-phenyl[1-14C]propan-1-ol ([14C]norephedrine) was administered orally to man, rat and rabbit and the metabolites excreted in the urine were identified and measured. Pronounced species differences in the metabolism of the drug were found. 2. Three male human subjects, receiving 25mg each of [14C]norephedrine hydrochloride, excreted over 90% of the14C in the first day. The main metabolite was the unchanged drug (86% of the dose) and minor metabolites were hippuric acid and 4-hydroxynorephedrine. 3. In rats given 12mg of the drug/kg almost 80% of the14C administered was excreted in the first day. The major metabolites in the urine were the unchanged drug (48% of the dose), 4-hydroxynorephedrine (28%) and trace amounts of side-chain degradation products. 4. Rabbits given 12mg of the drug/kg excreted 85–95% of the dose of14C in the urine in the first 24h after dosing. The major metabolites in the urine were conjugates of 1,2-dihydroxy-1-phenylpropane (31% of the dose) and of 1-hydroxy-1-phenylpropan-2-one (27%) and hippuric acid (20%). The unchanged drug was excreted in relatively small amounts (8%).

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

Hepatic uptake of intact glutathione S-conjugate, inhibition by organic anions, and sinusoidal catabolism

1993 ◽  
Vol 265 (3) ◽  
pp. G547-G554
Author(s):  
C. A. Hinchman ◽  
A. T. Truong ◽  
N. Ballatori
Keyword(s):  
Guinea Pig ◽  
Rat Liver ◽  
Marked Decrease ◽  
Hepatic Uptake ◽  
Half Time ◽  
High Concentrations ◽  
Rat Livers ◽  
Dose Dependent ◽  
Uptake And Metabolism ◽  
Guinea Pig Liver

To identify potential mechanisms for hepatic removal of circulating glutathione (GSH) conjugates, uptake and metabolism of S-2,4-dinitrophenylglutathione (DNP-SG) were examined in isolated perfused livers from rat and guinea pig. Guinea pig livers perfused with 5 mumol of DNP-SG in a recirculating system (50 microM initial concn) rapidly cleared the conjugate from the perfusate (half time 3.7 min), whereas clearance was considerably slower in rat liver (half time 35 min). Disappearance of DNP-SG from the perfusate was accompanied by a simultaneous appearance of DNP-SG and its metabolites in bile. Addition of acivicin, an inhibitor of gamma-glutamyltransferase (gamma-GT), to the perfusate resulted in a marked decrease in DNP-SG clearance by guinea pig liver but had no effect in rat liver, suggesting that in the guinea pig this process is largely dependent on sinusoidal gamma-GT activity. However, even in the presence of acivicin, rat and guinea pig livers removed nearly one-half of the administered DNP-SG from the recirculating perfusate over 30 min. High concentrations of DNP-SG were found in bile (up to 3.7 mM), indicating that the liver is capable of transporting the intact conjugate from the circulation. When rat livers were perfused with higher concentrations of DNP-SG (100 and 250 microM), biliary excretion of DNP-SG increased dose dependently, with concentrations in bile reaching 10 mM at the higher dose. This was accompanied by a dose-dependent choleresis.(ABSTRACT TRUNCATED AT 250 WORDS)

SPECIES DIFFERENCES IN THE DEOXYRIBONUCLEIC AND RIBONUCLEIC ACID CONTENTS OF LIVERS OF NON-PREGNANT AND PREGNANT MICE, GUINEA-PIGS AND CATS

1953 ◽  
Vol 9 (1) ◽  
pp. 45-51 ◽  
Author(s):  
ROSA M. CAMPBELL ◽  
H. W. KOSTERLITZ
Keyword(s):  
Guinea Pig ◽  
Protein Content ◽  
Liver Cell ◽  
Ribonucleic Acid ◽  
Guinea Pigs ◽  
Deoxyribonucleic Acid ◽  
Species Differences ◽  
Liver Cells ◽  
Maternal Liver ◽  
Pregnant Mice

1. The protein content of liver cells is almost independent of the size of the animal (mice, cats and previous results on rats, Campbell & Kosterlitz [1949]), and varies with the amount of protein eaten. 2. As has already been shown for rats, the ribonucleic acid ('RNA') content of the liver cells of non-pregnant mice, guinea-pigs and cats varies directly with the protein content of the cells. For a given protein content the mouse and rat have more RNA than the guinea-pig and cat. 3. During pregnancy there is a rise of the deoxyribonucleic acid ('DNA') content of the livers and in the protein content of the liver cells of mice (and rats), but not of guinea-pigs. 4. An excess of RNA over that predicted from the protein content of the liver cell has previously been found for the rat during pregnancy, and ascribed to the action of a placental factor on the maternal liver. A similar excess of RNA has now been observed in the mouse and, to a less extent, in the guinea-pig. It appears to be absent in the cat. 5. Possible causes of some of these species differences are considered.

Glutathione depletion inhibits amylase release in guinea pig pancreatic acini

1983 ◽  
Vol 244 (3) ◽  
pp. G273-G277
Author(s):  
W. F. Stenson ◽  
E. Lobos ◽  
H. J. Wedner
Keyword(s):  
Guinea Pig ◽  
Reduced Glutathione ◽  
Glutathione Depletion ◽  
Amylase Secretion ◽  
Ionophore A23187 ◽  
Amylase Release ◽  
Pancreatic Acini ◽  
Stimulus Secretion Coupling ◽  
Dose Dependent ◽  
Higher Doses

Isolated guinea pig pancreatic acini were specifically depleted of glutathione by treatment with 2-cyclohexene-1-one (2-CHX-1). Untreated acini contained 4.3 +/- 0.6 micrograms of glutathione per milligram protein. Incubation with 1 mM 2-CHX-1 for 5 min at 37 degrees C depleted glutathione to 17% of control values; 5 mM 2-CHX-1 depleted glutathione to less than 4% of control values. Incubation with 2-CHX-1 also impaired the ability of the isolated acini to secrete amylase in response to stimulation with carbachol and the ionophore A23187. The depletion of glutathione and the inhibition of amylase secretion by 2-CHX-1 were both dose dependent and time dependent. Incubation of acini with 2 mM 2-CHX-1 for 15 min at 37 degrees C reduced glutathione levels to 6.6% of control and reduced carbachol-stimulated amylase release to 63% of control. Higher doses of 2-CHX-1 or longer incubations resulted in greater depletion of glutathione and greater inhibition of carbachol-induced amylase release. These data indicate that specific depletion of glutathione impairs the ability of isolated acini to secrete amylase in response to physiological and pharmacologic stimuli and suggest that glutathione has a role in stimulus-secretion coupling in the exocrine pancreas.

scholarly journals Effects of corn silk aqueous extract on intraocular pressure of ocular hypertensive human subjects

2013 ◽  
Vol 72 (3) ◽  
Author(s):  
G.O. George ◽  
F.K. Idu ◽  
L.F.O. Obika
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Intraocular Pressure ◽  
Aqueous Extract ◽  
Zea Mays L ◽  
Human Subjects ◽  
Hypotensive Effect ◽  
Peak Effect ◽  
Corn Silk ◽  
Dose Dependent

Stigma/style of Zea mays L (Corn silk) has been documented to have hypotensive effect on blood pressure and to relieve oedema. However we are not aware of any literature on its hypotensive effect on intraocular pressure (IOP) of humans or animals. We studied the effects of water only, masked doses of corn silk aqueous extract (60 mg/kg, 130 mg/kg, 192.5 mg/kg and 260 mg/kg body weight) on the IOP and blood pressure (BP) of twenty normotensives and twenty ocular hypertensive subjects. Also we compared the effects of the varied doses of corn silk aqueous extract (CSAE) with masked doses (5 mg/kg and 10 mg/kg body weight) of acetazolamide on IOP of ocular hypertensive subjects only. The results showed that the last three doses of CSAE lowered IOP and BP significantly (p<0.001) within eight hours of administration. The peak effect on IOP was observed after four hours while the peak effect on BP was observed after three hours of administration in the normotensives and ocular hypertensive subjects likewise the hypotensive effect was dose-dependent. The results also showed that 130 mg/kg body weight of CSAE produced the same hypotensive effect on IOP of ocular hypertensive subjects as 5 mg/kg body weight of acetazolamide. Therefore CSAE may have some IOP lowering effects that require further investigation in the management of ocular hypertension. (S Afr Optom 2013 72(3) 133-143)

Neurokinin receptor mediated plasma extravasation in guinea pig and rat airways: comparison of 125I-labelled human fibrinogen and 99mTc-labelIed human serum albumin as markers of leakage

1993 ◽  
Vol 71 (7) ◽  
pp. 506-511 ◽  
Author(s):  
Christine Tousignant ◽  
Chi-Chung Chan ◽  
Donna Young ◽  
Diane Guevremont ◽  
Ian W. Rodger
Keyword(s):  
Human Serum Albumin ◽  
Guinea Pig ◽  
Serum Albumin ◽  
Human Serum ◽  
Plasma Extravasation ◽  
Human Fibrinogen ◽  
Protein Extravasation ◽  
Neurokinin Receptor ◽  
Lower Airways ◽  
Dose Dependent

In the present study we have characterized NK-1 and NK-2 receptor induced microvascular leakage in guinea pig and rat airways, using 125I-labelled human fibrinogen ([125I]FN) versus 99mTc-labelled human serum albumin ([99mTc]HSA) as markers for plasma protein extravasation. Intravenous administration of the selective NK-1 agonist [Sar9, Met(O2)11]SP (1 nmol kg−1) caused a dose-dependent increase of [125I]FN extravasation in guinea pig trachea, main bronchi, secondary bronchi, and intraparenchymal airways. Extravasation of [125I]FN increased by up to 192 (trachea), 284 (main bronchi), 368 (secondary bronchi), and 271% (intraparenchymal bronchi) over control levels in these regions of the airways. Pretreatment of the animals with CP 99,994 and RP 67,580, two NK-1 nonpeptide antagonists, caused a dose-dependent inhibition of [Sar9, Met(O2)11]SP-induced leakage of [125I]FN. [Sar9, Met(O2)11]SP (1 nmol kg−1) did not induce specific leakage of [99mTc]HSA in the intraparenchymal bronchi. Specific NK-2 receptor induced leakage was detected in the lower airways but only when using [125I]FN as a marker. We have also compared the ability of CP 99,994 and RP 67,580 to inhibit [Sar9, Met(O2)11]SP induced extravasation of [125I]FN in rat airways. CP 99,994 was 40–50 (tracheobronchial region) to 75 (lower airways) times more potent in the guinea pig than the rat airways. In contrast, RP 67,580 had higher affinity for rat airways compared with guinea pig airways. The results of this study highlight the superiority of [125I]FN as a sensitive marker of plasma extravasation over [99mTc]HSA. Furthermore, the results strongly suggest that both NK-1 and NK-2 receptors mediate plasma extravasation in the guinea pig lower airways and that NK-1 receptors are different in guinea pig and rat airways.Key words: Leakage, tachykinins, NK-1 and NK-2 receptors, airway, asthma.

Sign in / Sign up

Export Citation Format

Share Document