norpseudoephedrine and Body-Weight

To investigate the efficacy and safety of increasing doses of cathine (nor-pseudoephedrine) as a weight-lowering agent in patients with obesity.. Overweight and obese patients (n = 241, mean BMI 34.6 ± 3.4 kg/m²) were randomly allocated to one of three doses of cathine (16 mg, 32 mg, 53.3 mg) or placebo in addition to a multimodal lifestyle intervention program in a multicenter, double-blind, controlled, dose-finding study for 24 weeks. Primary outcome was weight loss.. Treatment with the 3 doses of cathine resulted in a significantly greater weight loss compared to placebo over 24 weeks: 6.5 ± 4.2 kg for 16 mg cathine, 6.2 ± 4.7 kg for 32 mg cathine, and 9.1 ± 5.4 kg for 53.3 mg cathine versus 2.4 ± 4.4 kg for placebo (each p < 0.01, ANCOVA). The percentage of patients losing > 5% / >10% of initial body weight was significantly greater for all doses of cathine than for placebo (each p < 0.01, chi-square test). Heart rate increased dose-dependently (by 1.2 bpm under 16 mg, 5.8 bpm under 32 mg, and 6.2 bpm under 53.3 mg cathine), but no suspected unexpected serious adverse reactions were noted. The overall dropout rate was 24.9%, with the highest rate in the placebo group (42.3%).. Cathine appears to be an effective weight-lowering agent for adjunct treatment of obesity, but additional clinical studies on its efficacy and safety are required.

Topics: Adult; Anti-Obesity Agents; Body Mass Index; Body Weight; Double-Blind Method; Female; Heart Rate; Humans; Male; Middle Aged; Obesity; Overweight; Phenylpropanolamine; Placebos; Weight Loss

Topics: Aged; Body Weight; Clinical Trials as Topic; Double-Blind Method; Ephedrine; Female; Humans; Male; Middle Aged; Obesity; Phenylpropanolamine; Stereoisomerism

-(-)-Norpseudoephedrine (NPE), the enantiomer of cathine and a structural analog of phenylpropanolamine, shows anorectic and antidipsic effects that have been referred to its structural analogies with amphetamine. When amphetamine is chronically administered to rats, its anorectic effects fade out, water intake is progressively increased, and the diuretic response to the drug remains stable. Our previous studies show that chronic administration of NPE does not produce the typical amphetamine hyperdipsic response. In the present study, designed to obtain a more detailed picture of the ingestive and diuretic effects of chronic exposure to NPE, we evaluated the effects of 11 daily administrations of three doses of NPE (17, 32, and 56 mg/kg IP) on food and water intake, as well as on diuresis, in rats maintained in conditions of free access to food and water. Results show that all three doses inhibited food intake at 2 h, whereas only the highest dose inhibited food intake at 5 h. No differences between groups were detected at 24 h. These responses remained unchanged throughout the 11 days of treatment, and substitution of NPE with a solvent injection caused no rebound feeding. NPE treatment did not modify the ingestive response to a challenge injection of amphetamine, 0.56 and 1.0 mg/kg IP, given 1 day apart. Although NPE inhibited water intake throughout the experiment, it did so significantly only during the first 2 h postinjection. Urine output in the NPE-treated groups increased significantly on the first day only. These findings make it unlikely that the anorectic effects of NPE depend on an amphetamine-like mechanism of action. In addition, the short-lasting anorectic and antidipsic effects of NPE and the lack of tolerance to them raise the possibility of a therapeutic use of this drug as an adjuvant in the therapy of eating disorders characterized by binge episodes.

Topics: Amphetamine; Animals; Appetite Depressants; Body Weight; Diuresis; Drinking Behavior; Drug Tolerance; Eating; Feeding Behavior; Male; Phenylpropanolamine; Rats; Rats, Sprague-Dawley

In order to investigate effects of khat chewing on uteroplacental blood flow (+)norpseudoephedrine (NPE) infusions were given to 11 anesthetized guinea pigs in late pregnancy (62-66 days) after unilateral uterine artery ligation at days 30-32. Regional blood flows were determined with radioactive microspheres. Mean arterial blood pressure increased with 25% and heart rate with 9% during NPE infusion. Myoendometrial blood flow was reduced by 31%. Placental vascular resistance (PVR) increased by 56% in the control horn (17 fetuses) and by 82% in the ligated horn (17 fetuses). This vasoconstriction was counteracted by the systemic vasopressor response since placental blood flow remained unchanged. When considering only the 13 growth-retarded fetuses, however, PVR increased by 98% and a 19% reduction of placental blood flow could be demonstrated. These results suggest that the placenta of the growth-retarded fetus may be more sensitive to adrenergic stimulation than the normal placenta. Furthermore, since one of the active constituents of khat, (+)norpseudoephedrine, causes vasoconstriction in the uteroplacental vascular bed it is possible that khat chewing could reduce placental blood flow and, as a consequence, impair fetal growth.

Topics: Animals; Appetite Depressants; Body Weight; Cardiac Output; Catha; Female; Fetus; Guinea Pigs; Hemodynamics; Male; Organ Size; Phenylpropanolamine; Placenta; Plant Extracts; Pregnancy; Regional Blood Flow; Uterus; Vascular Resistance

The anorexigenic effects of cathine (phenylpropanolamine) and cathinone (alpha-aminopropiophenone), both amines obtained from Catha edulis Forsk. (Khat) were investigated by acute and chronic experiments in rats. Amphetamine was included for comparison purposes. Both khat amines reduced food intake when administered acutely and body weight when given chronically. Cathinone was more effective than cathine, and both were less active than amphetamine. Partial or total cross-tolerance was observed among the 3 drugs.

Topics: Alkaloids; Amphetamine; Animals; Appetite Depressants; Body Weight; Drug Tolerance; Eating; Phenylpropanolamine; Plants, Medicinal; Propiophenones; Rats