norpseudoephedrine and cathinone

Khat, Catha edulis Forsk, is among the most widely used plant-based psychoactive substance in the world. Grown in Eastern Africa, Horn of Africa, and southwestern part of the Arabian Peninsula, its fresh young leaves and twigs are used daily by over 20 million people for the psychostimulatory effects it produces in the user, a practice deeply rooted in the history, tradition, and culture of the indigenous population. Once hardly known outside the regions where it is grown and used, khat use has now spread to other countries. This review will cover the, phytochemistry, pharmacokinetics of the active ingredients-cathinone, cathine, norephedrine, neurochemistry, effects on cognitive and executive functions as well as its ability to produce dependency in the user. Whether it is an innocuous cultural practice or a drug of abuse is debatable as the preclinical and clinical data needed to arrive at an authoritative conclusion is lacking.

Topics: Alkaloids; Brain; Catha; Child Development; Cognition; Humans; Infant; Phenylpropanolamine; Psychoses, Substance-Induced; Substance-Related Disorders

Although there is a rich body of research available regarding the effect of acute and chronic khat dosing in animal models, research on the behavioral and cognitive effects of khat in human subjects is not extensive and several of the available studies have been done only in the context of observational and single-case studies. In light of the absence of a substantial literature on the neurobehavioral deficits associated with khat use and to provide a context that could be used to identify themes for future research we review previous research that has focused on other stimulant drugs. This review highlights multiple areas of neurocognitive deficit that have been identified in previous studies of individuals who have been chronic users of stimulants, such as amphetamines and methamphetamines. The review highlights a substantial body of evidence demonstrating a wide range of learning and memory impairments including deficits that persist during abstinence from active drug use. This review does not imply a similar khat effect, but due to some similarities pharmacologically between the active components of khat (cathinone and cathine) and amphetamines, future studies examining these same domains of cognitive functioning in chronic khat users and abstinent khat users appears to be warranted, if possible using some of the same or similar laboratory measures.

Topics: Alkaloids; Amphetamines; Catha; Central Nervous System Stimulants; Cognition; Humans; Phenylpropanolamine; Plant Leaves; Psychotropic Drugs; Substance Withdrawal Syndrome; Substance-Related Disorders

Several phenylethylamines are under consideration for international control. The effects of repeated administration of these compounds, including tolerance, physical dependence and central nervous system (CNS) toxicity, are reviewed here. The compounds can be divided into two major chemical groups: those with substituents on the ethylamine portion of the molecule and those with substituents on the phenyl ring. Although the effects of repeated administration have not been directly determined for most of the compounds, certain representative compounds of each chemical group have been examined in some detail. Prominent among the effects of repeated administration are CNS toxicity and tolerance development. Physical dependence has not been reported for any of these compounds. Future research with these compounds should emphasize the investigation of the CNS toxicity and the functional consequences of such effects for the organism.

Topics: 3,4-Methylenedioxyamphetamine; Alkaloids; Amphetamines; Animals; Central Nervous System; Central Nervous System Diseases; Chemical Phenomena; Chemistry; Corpus Striatum; Dogs; Dopamine; Drug Tolerance; Humans; In Vitro Techniques; Macaca mulatta; Norepinephrine; Phenethylamines; Phenylpropanolamine; Rabbits; Rats; Serotonin; Substance-Related Disorders; Synaptic Transmission; Synaptosomes

Topics: Alkaloids; Amphetamine; Animals; Behavior; Catha; Central Nervous System Stimulants; Dopamine; Humans; Norepinephrine; Phenylpropanolamine; Plant Extracts; Receptors, Dopamine; Serotonin; Substance-Related Disorders

Topics: Alkaloids; Animals; Catha; Dextroamphetamine; Female; Humans; Male; Mice; Motor Activity; Phenylpropanolamine; Plant Extracts; Social Behavior; Stereoisomerism; Stereotyped Behavior; Substance-Related Disorders

Twenty-four adult male Wistar albino rats (250-300 g) were randomly selected and divided into six groups of four rats each. All groups received a single oral dose of 2,000 mg/kg body weight, and blood and tissue samples from the brain, lung, heart, liver, and kidney were obtained at intervals of 0.5, 1, 2.5, 5, 12, and 24 h. The cathine and cathinone concentrations were identified and quantified using ion trap ultra-high performance liquid chromatography (HPLC-IT/MS). The neurotransmitter profile was detected using the quadrupole time of flight UPLC-QTOF/MS method.. The lung, liver, and heart tissues attained the highest levels of cathine, while the highest level of cathinone was determined in the heart. Cathine and cathinone concentrations in the blood and heart peaked at 0.5 h. The concentrations peaked in the brain 2.5 h later, indicating that the heart had an immediate effect, whereas the brain had a longer-lasting one. They have longer half-lives (2.68 and 5.07 h, respectively) and may remain in the brain for longer durations (3.31 and 2.31 h, respectively). The neurotransmitters epinephrine, dopamine, norepinephrine, and serotonin were detected in a delayed, prolonged and organ-specific manner.. Cathine and cathinone were deposited in considerable concentrations in all tissues analyzed, with the highest C

Topics: Animals; Catha; Dopamine; Epinephrine; Kinetics; Norepinephrine; Plant Extracts; Rats; Rats, Wistar; Serotonin

The consumption of Khat leaves represents an ancient kind of drug abuse mainly observed in Eastern Africa and the Arab Peninsula among adult men. For this purpose, the leaves are directly collected from the shrub "Catha edulis" prior to extensive chewing process. Seizures in Europe are rare, since the leaves have to undergo quick transportation: After a short period of time, the harvested leaves decompose and suffer in decrease of concentration of the active ingredient cathinone, which makes long term transportation difficult. As an alternative, plant material can be dried to increase life period. In the past years, an increasing number of seizures were made by Austrian police, however, the content of cathinone and cathine in dry material is widely unknown. In this work, a seizure of fresh Khat leaves was compared with two seizures of dried material in terms of concentration of cathinone and cathine using LC-MS/MS analysis. For fresh leaves, a purity grade was found to be 0.115-0.158% for cathinone and 0.172-0.192% for cathine, respectively. In contrast, subsequent storage of dried Khat leaves over months led to a dramatic loss of cathinone: Analysis of two seizures revealed that concentration of cathinone dropped to 0.021-0.023%. These findings are intended to serve as a guideline for Justice authorities to estimate the content of the controlled ingredients of Khat leaves in future.

Topics: Alkaloids; Catha; Chromatography, Liquid; Desiccation; Humans; Phenylpropanolamine; Plant Leaves; Substance-Related Disorders; Tandem Mass Spectrometry

Until recently, there was rather little interest in the structure-activity relationships (SARs) of cathinone analogs because so few agents were available and because they represented a relatively minor drug abuse problem. Most of the early SAR was formulated on the basis of behavioral (e.g., locomotor and drug discrimination) studies using rodents. With the emergence on the clandestine market in the last few years of a large number of new cathinone analogs, termed "synthetic cathinones", and the realization that they likely act at dopamine, norepinephrine, and/or serotonin transporters as releasing agents (i.e., as substrates) or reuptake inhibitors (i.e., as transport blockers), it has now become possible to better examine their SAR and even their quantitative SAR (QSAR), in a more effective and systematic manner. An SAR picture is beginning to emerge, and key structural features, such as the nature of the terminal amine, the size of the α-substituent, stereochemistry, and the presence and position of aromatic substituents, are being found to impact action (i.e., as releasing agents or reuptake inhibitors) and transporter selectivity.

Topics: Adrenergic Uptake Inhibitors; Alkaloids; Amphetamines; Animals; Central Nervous System Stimulants; Dopamine Uptake Inhibitors; Humans; Phenylpropanolamine; Propiophenones; Selective Serotonin Reuptake Inhibitors; Structure-Activity Relationship; Substance-Related Disorders

A literature criticism is given on methods using currently gas chromatography mass spectrometry (GC/MS) to determine cathine (CAT), cathinone (CTN) and norephedrine (NE), jointly khatamines. In this study, khatamines' oximation, trimethylsilylation and mass fragmentation properties-applying N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA), its trimethyliodosilane (TMIS) catalyst containing version (MSTFA(TMIS)), N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and hexamethyldisilazane (HMDS)-was highlighted, at first. Derivatization, mass fragmentation and quantitation related, optimized model investigations have been carried out as a function of the reaction times and conditions. Special emphasis was put (i) on the stability of the primarily formed (CAT-2TMS, NE-2TMS, CTN-TMS(TMS-oximes)1,2), then transformed, fully derived (CAT-3TMS, NE-3MTS, CTN-2TMS(TMS-oximes)1,2) species, and, (ii) on the proportionally formed stable products, suitable to selective quantitation of all three natural amines, simultaneously. Results, as novelty to the field confirmed that (i) TMIS catalyzed trimethylsilyation triggers to form fully derivatized species unfortunately, in part only; while, (ii) khatamines' simultaneous quantitation needs to be carried out in a two steps derivatization process consisting of oximation (1st step, hydroxylamine in pyridine) and trimethylsilylation (2nd step, MSTFA), to the CAT-2TMS, NE-2TMS, CTN-TMS(TMS-oximes)1,2. These species were characterized with their retention, mass fragmentation and analytical performance properties, in model solutions and in the presence of plant tissues, as well: R(2), limit of quantitation (LOQ) data, expressed in pg/1μL injection basis, proved to be 62.5pg (CAT), 20pg (NE) and 62.5pg (CTN), respectively. The practical utility of proposal was enormously enhanced by the novel, direct sample preparation method. In this process, the freshly harvested, freeze-dried, then pulverized leaves of Catha edulis FORKS were directly derivatized, in the presence of the matrix. Reproducibility (in average 2.07 RSD% varying between 0.15 and 5.5 RSD%), linearity (0.9990-0.9994) and recovery (95.7-99.1%) values of the new sample preparation protocol was confirmed by the standard addition method for CAT, NE and CTN equally. From plant leaf, 0.061w/w% CAT and 0.014w/w% NE contents were obtained. In this tissue CTN was not found. Very likely attributable to the unfavorable climate for the plant: grown in Hungary of temperate zon

Topics: Acetamides; Africa; Alkaloids; Catha; Chemistry Techniques, Analytical; Fluoroacetates; Gas Chromatography-Mass Spectrometry; Organosilicon Compounds; Phenylpropanolamine; Reproducibility of Results; Trimethylsilyl Compounds

The stimulating herbal drug khat (cathine, cathinone) and its analog methcathinone are common substances of abuse in most countries. A GC-MS method was developed and validated for the detection and quantification of cathine, cathinone, methcathinone and ephedrine in oral fluid specimens. The analytes and internal standard (amphetamine-d5) were extracted from 0.5 mL oral fluids by ethyl acetate, and then the dried extracts were derivatized with heptafluorobutyric anhydride at 70°C for 30 min. The MS was used in selected ion monitoring mode. Ions monitored were m/z 117, 240 and 330 for cathine, m/z 77, 105 and 240 for cathinone, m/z 105, 210 and 254 for methcathinone, m/z 210, 254 and 344 for ephedrine and m/z 244 and 336 for amphetamine-d5 The calibration curves were linear (r(2)> 0.98) in the concentration range 20-2,000 ng/mL for all analytes. The intra- and inter-assay imprecisions were within (1.6-12.5%) and (1.5-9.5%), respectively, for all analytes. Intra-assay accuracies were between -5.9 and 6.7% for all analytes. The method was successfully applied to detect and quantify the target analytes from oral fluid specimens collected from Khat and methcathinone users.

Topics: Alkaloids; Central Nervous System Stimulants; Chemistry, Clinical; Ephedrine; Gas Chromatography-Mass Spectrometry; Humans; Illicit Drugs; Phenylpropanolamine; Propiophenones; Reproducibility of Results; Saliva

A capillary electrophoretic method, which allowed the detection and separation of the active principles of Catha edulis, i.e. cathinone, cathine and phenylpropanolamine, was developed. A suitable internal standard (nicotinamide), which permitted the quantification of the analytes reducing the variability of the migration times due to EOF changes, was identified. The analytical method was validated, assessing linearity, sensitivity and repeatability, showing optimal features for the analysis of the vegetable material. Moreover extraction conditions were investigated to achieve the exhaustion of the plant material in the fastest and most efficient way to meet the requirements of the Court.

Topics: Alkaloids; Catha; Electrophoresis, Capillary; Molecular Structure; Phenylpropanolamine; Plant Extracts; Reproducibility of Results

The GC method previously reported by our research group for the analysis of the active principles of Catha edulis, i.e. cathine, cathinone and phenylpropanolamine, was considerably improved. N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA) as derivatizing agent was employed, thus allowing an accurate determination of the analytes and a suitable internal standard for quantitative analyses (nicotinamide) was introduced. Moreover the chromatographic conditions were carefully studied to improve the separation of the alkaloids and sensitivity. To this end different chromatographic capillary columns and temperature gradients were investigated. The optimized GC method was validated and resulted adequate for the application in forensic analysis. Finally on behalf of the Tribunal, C. edulis vegetable material seized by the police in northern Italy was analyzed, the quantity of cathine ranging from 0.095 to 0.29%, the quantity of PPA from 0.010 to 0.21% and the quantity of cathinone from 0.025 to 0.374% of the weight of the vegetable material.

Topics: Alkaloids; Catha; Gas Chromatography-Mass Spectrometry; Italy; Phenylpropanolamine

Amphetamine and amphetamine derivatives are suggested to induce an immunosuppressive effect. However, knowledge of how amphetamines modulate intracellular signaling pathways in cells of the immune system is limited. We have studied phosphorylation of signal transduction proteins (Akt, CREB, ERK1/2, NF-κB, c-Cbl, STAT1/3/5/6) and stress sensors (p38 MAPK, p53) in human leukocyte subsets following in vitro treatment with the natural amphetamine cathinone, the cathinone derivatives cathine and norephedrine, in comparison with a defined extract of the psychostimulating herb khat (Catha edulis Forsk.). Intracellular protein modifications in single cells were studied using immunostaining and flow cytometry, cell viability was determined by Annexin V-FITC/Propidium Iodide staining, and T-lymphocyte proliferation was measured by (3)H-thymidine incorporation.. Cathinone, cathine and norephedrine generally reduced post-translational modifications of intracellular signal transducers in T-lymphocytes, B-lymphocytes, natural killer cells and monocytes, most prominently affecting c-Cbl (pTyr700), ERK1/2 (p-Thr202/p-Tyr204), p38 MAPK (p-Thr180/p-Tyr182) and p53 (both total p53 protein and p-Ser15). In contrast, the botanical khat-extract induced protein phosphorylation of STAT1 (p-Tyr701), STAT6 (p-Tyr641), c-Cbl (pTyr700), ERK1/2 (p-Thr202/p-Tyr204), NF-κB (p-Ser529), Akt (p-Ser473), p38 MAPK (p-Thr180/p-Tyr182), p53 (Ser15) as well as total p53 protein. Cathinone, cathine and norephedrine resulted in unique signaling profiles, with B-lymphocytes and natural killer cells more responsive compared to T-lymphocytes and monocytes. Treatment with norephedrine resulted in significantly increased T-lymphocyte proliferation, whereas khat-extract reduced proliferation and induced cell death.. Single-cell signal transduction analyses of leukocytes distinctively discriminated between stimulation with cathinone and the structurally similar derivatives cathine and norephedrine. Cathinone, cathine and norephedrine reduced phosphorylation of c-Cbl, ERK1/2, p38 MAPK and p53(Ser15), and norephedrine induced T-lymphocyte proliferation. Khat-extract induced protein phosphorylation of signal transducers, p38 MAPK and p53, followed by reduced cell proliferation and cell death. This study suggests that protein modification-specific single-cell analysis of immune cells could unravel pharmacologic effects of amphetamines and amphetamine-like agents, and further could represent a valuable tool in elucidation of mechanism(s) of action of complex botanical extracts.

Topics: Alkaloids; Catha; Cell Proliferation; Cell Survival; Cells, Cultured; Humans; Leukocytes, Mononuclear; Phenylpropanolamine; Plant Extracts; Signal Transduction

In recent years, synthetic cannabinoids have been frequently observed in seized materials all over the world. This new generation of designer drugs, mixed with herbal substances, is also known as "Herbal Highs" or "Legal Highs". There are many articles about the history, type and pharmaco-chemical properties of synthetic cannabinoids in the literature; however the number of articles about the frequency of their detection is limited. In this study, we evaluated the type and detection frequency of synthetic cannabinoids in Istanbul and its surrounding area. The reports of the Council of Forensic Medicine-Istanbul Narcotic Department were retrospectively reviewed for the presence of synthetic cannabinoids in herbal compounds sent by the judicial authorities between August 01, 2010 and March 31, 2012. Among 1200 herbal compounds, 1179 of them (98.3%) contained synthetic cannabinoids. Twenty-one samples (1.7%) had other psychoactive substances. The analysis of 1179 samples showed that JWH-018 was present in 1172 (99.4%) of the samples. JWH-081 was found in 777 samples (65.9%) together with JWH-018. Samples had different package names. "Bonzai Aromatic Potpourri" (n = 755; 64.0%) and "Bonzai Plant Growth Regulator" (n = 316; 26.8%) were the most common product names amongst the herbal products in this study. It is clear from the present study and previous studies that brand name of synthetic cannabinoids that dominate the market exhibit regional differences as to the type and detection frequency of synthetic cannabinoids and the content of herbal highs packages. The number and diversity of synthetic cannabinoid compounds have increased dramatically in the drug market in recent years. New, different, potent derivatives appear on the market almost every day and this presents important problems that need to be solved by scientists and judicial authorities working to prevent their harm. These problems include the limited knowledge about their frequency, the lack of analytical data and reference standards for analysis of these new derivates, the lack of information on their toxic effects, and information about the metabolism and metabolites for toxicological analysis in human subjects.

Topics: Alkaloids; Cannabinoids; Designer Drugs; Forensic Toxicology; Humans; Indoles; Methamphetamine; Naphthalenes; Phenylpropanolamine; Plant Preparations; Psychotropic Drugs; Retrospective Studies; Turkey

In the last years, all the vegetable material supposed to belong to the Catha Edulis species, seized at the Malpensa and Orio al Serio airports, were analyzed in our laboratory on behalf of the Tribunals of Busto Arsizio and Bergamo, respectively. After a preliminary botanic examination, the quali-quantitative determination of the active principles cathinone, cathine and phenylpropanolamine (PPA) was carried out by means of GC/MS and GC/FID techniques, which meet the requirements of the forensic analyses. We developed a fast, effective and reliable derivatization procedure which allowed to simultaneously detect cathine and PPA, whose discrimination is mandatory since PPA is not a psychoactive agent. Cathine was distributed in the various parts of the plant (leaves and stems) and its quantity ranged from 0.03% to 0.17% of the weight of the vegetable material; PPA was not detected in the twigs and its quantity in the leaves ranged from 0.07% to 0.16%. The quantitative determination of cathinone was carried out directly on the methanol solution after maceration of the vegetable material, its quantity ranging from 0.02% to 0.10%. No significant difference in the content of the two active principles was found between the fresh and the dried material.

Topics: Alkaloids; Catha; Central Nervous System Stimulants; Desiccation; Flame Ionization; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Phenylpropanolamine; Plant Leaves; Plant Stems

Khat chewing amongst the UK communities originating from Yemen and the East African coast is suggested to create dependency through its main stimulant components (cathinone, norephedrine and norpseudoephedrine) on the central nervous system.. To validate self-reported khat chewing behaviours by measuring levels of cathinone, norephedrine and norpseudoephedrine in saliva and to explore their associations with self-reported khat chewing dependency.. Face-to-face interviews were conducted amongst 30 male UK-resident khat chewers. Saliva samples were collected from each participant and high-performance liquid chromatography (HPLC) employed to extract and quantify the levels of the biomarkers.. The mean (SD) for cathinone and the composite norephedrine and norpseudoephedrine levels were 33.93 (±39.20) and 29.28 (±26.32)μg/mL respectively. These biomarkers were significantly associated (p≤0.05) with khat chewing dependency.. Validation of self-reported khat chewing is possible. Khat chewing dependency correlates significantly with biomarker levels in saliva. Replication is required.

Topics: Adult; Africa; Alkaloids; Biomarkers; Catha; Central Nervous System Stimulants; Chromatography, High Pressure Liquid; Dangerous Behavior; Disclosure; Humans; Interviews as Topic; Male; Mastication; Middle Aged; Phenylpropanolamine; Plant Preparations; Reproducibility of Results; Saliva; Self Report; Substance-Related Disorders; United Kingdom; Yemen

A primary concern with the forensic analysis of the khat plant (Catha edulis) has been the need to preserve the principle psychoactive component, cathinone, which converts to the less-active substance, cathine, after harvesting. The loss of cathinone has serious legal implications since it is a Schedule I controlled substance under federal regulations in the United States, while cathine is Schedule IV. A common misconception is that cathinone is highly unstable once the plant is harvested, and may be undetectable upon drying and prolonged storage. However, drying the plant material will preserve cathinone. Numerous seizures of a dried form of khat (referred to as "graba" in the United States) have been made in recent years, suggesting that drying the plant material is a viable approach to preserve khat evidence for both storage and reanalysis. A qualitative and quantitative study of the composition of khat samples seized as dried plant material has found the khat alkaloids to be relatively stable for a monitored period of 3 years, and cathinone has remained identifiable while stored at room temperature for over 10 years. Studies of green khat (received moist) have also determined that drying the moist leaves at either room temperature or by the application of heat are suitable methods to preserve cathinone in the dried material. These findings demonstrate that cathinone persists in dried khat for a time frame of several years, and simple drying techniques are an effective means to preserve seized khat evidence for long-term storage.

Topics: Alkaloids; Catha; Central Nervous System Stimulants; Chromatography, High Pressure Liquid; Desiccation; Drug Stability; Ephedrine; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Linear Models; Molecular Structure; Phenylpropanolamine; Plant Leaves; Specimen Handling

Hallucinogenic mushrooms (e.g. Psilocybe and Panaeolus species) as well as leaves and young shoots of the khat tree (Catha edulis Forsk) are illicit drugs in many countries. The exact concentration of the hallucinogenic alkaloids psilocin and psilocybin in mushrooms and the sympathomimetic alkaloids cathinone and cathine in khat is usually essential for jurisdiction. Facing an increasing number of mushroom and khat seizures by German customs authorities, a convenient comprehensive quantitative HPLC method based on cation-exchange liquid chromatography for these rather "exotic" drugs has been developed which avoids time-consuming multi-step sample preparation or chemical derivatization procedures. Using this method a number of different hallucinogenic fungi species and products that are mainly distributed via the internet have been analysed (dried and fresh Psilocybe cubensis Singer as well as P. cubensis collected from "grow boxes", Panaeolus cyanescens Berkeley and Broome and so-called "philosopher stones" (sclerotia of Psilocybe species)). Highest total amounts of psilocin have been detected in dried P. cyanescens reaching up to 3.00+/-0.24 mg per 100 mg. The distribution of khat alkaloids in different parts of the khat shoots has been studied. High concentrations of cathinone have not only been detected in leaves but also in green parts and barks of stalks. Additionally, the sample treatment for fresh mushroom and khat samples has been optimised. Highest amounts of alkaloids were found when fresh material was freeze-dried.

Topics: Agaricales; Alkaloids; Catha; Central Nervous System Stimulants; Chromatography, Liquid; Desiccation; Forensic Toxicology; Freeze Drying; Hallucinogens; Illicit Drugs; Limit of Detection; Phenylpropanolamine; Plant Structures; Psilocybin

Topics: Alkaloids; Appetite Depressants; Catha; Developing Countries; Humans; Male; Miosis; Phenylpropanolamine; Psychotropic Drugs; Yemen

Khat is a plant whose young shoots and leaves are habitually used in Eastern Africa and the Arabian Peninsula as a drug of recreation. Although it is used without any control in these regions, it contains two controlled substances, cathinone (schedule I) which is present in fresh khat and cathine (schedule VI) which is a degradation product of cathinone abundant in old khat.. To determine the effect of khat on locomotor behaviour and seizures in rats.. Experimental study.. University of Nairobi.. Adult male rats in groups of six were given fresh khat, old khat, methylphenidate and saline at varying doses and observed over three hours.. Fresh khat at low doses and old khat at high doses stimulated locomotor activity. High doses of fresh and old khat induced stereotype behaviour and seizures.. The results show that khat stimulates locomotor and stereotypic behavioural activity and can induce seizures; results similar to those observed with amphetamine analogs.

Topics: Alkaloids; Analysis of Variance; Animals; Behavior, Animal; Catha; Dose-Response Relationship, Drug; Kenya; Male; Methylphenidate; Motor Activity; Observation; Phenylpropanolamine; Plant Preparations; Rats; Rats, Sprague-Dawley; Seizures; Stereotypic Movement Disorder; Time Factors

Khat (Catha edulis Forsk., Celastraceae) is a perennial shrub that was introduced to Israel by Yemenite immigrants. Khat young leaves are chewed as a stimulant. The main stimulating active principles in this plant are the phenylpropylamino alkaloids (-)-cathinone [(S)-alpha-aminopropiophenone], (+)-cathine [(+)-norpseudoephedrine] and (-)-norephedrine. A novel GC-MS analysis method for the quantitative determination of phenylpropylamino alkaloids and their putative precursor 1-phenyl-1,2-propanedione in khat leaves was developed. We found a marked diversity in the phenylpropylamino alkaloids content and composition in 9 different accessions originated in seedlings and in the commercial cultivar "Mahanaim". The highest 1-phenyl-1,2-propanedione and (-)-cathinone levels occur in young leaves, the part traditionally chewed for its psycho-stimulating properties. Older leaves lack (-)-cathinone but contain the less active (+)-cathine and (-)-norephedrine. Young stems and flowers also contain 1-phenyl-1,2-propanedione, (-)-cathinone, (+)-cathine and (-)-norephedrine. We report the presence of a (-)-cathinone reductase in khat leaves capable of reducing (-)-cathinone to (+)-cathine in the presence of NADPH. We propose that (-)-cathinone is a biosynthetic precursor of (+)-cathine and (-)-norephedrine in khat leaves.

Topics: Alkaloids; Catha; Phenylpropanolamine

A sensitive and reproducible method for the quantitative determination of cathinone (CTN), norpseudoephedrine (NPE, cathine) and norephedrine (NE) from hair was developed. The compounds were extracted for 4 hours with phosphate buffer pH 2.0, followed by a standard solid phase extraction procedure on a mixed phase column, derivatization with heptafluorobutyric anhydride (HFBA) and GC-MS separation and quantification using D(3)-ephedrine (D(3)-E) and alpha-aminoacetophenone (AAP) as the internal standards. The diastereomers NPE and NE were satisfactorily separated. In the validation, the limits of detection and of quantification were determined at 0.03-0.08 ng/mg and 0.10-0.24 ng/mg, respectively and the interday standard deviation was between 10 and 15%. The method was applied to hair samples of 24 Yemenite khat chewers. All three compounds were detected in 23 of these cases. The concentrations ranged from 0.57 to 23.9 ng/mg for NPE, 0.19-25.0 ng/mg for NE and 0.11-22.7ng/mg for CTN. A highly significant correlation was found between the self-reported data about the khat consumption habits of the volunteers (4-56h chewing per week) and the concentrations of norephedrine and norpseudoephedrine in hair.

Topics: Acetophenones; Alkaloids; Catha; Gas Chromatography-Mass Spectrometry; Hair; Humans; Molecular Structure; Phenylpropanolamine; Plant Extracts; Plant Leaves; Psychotropic Drugs; Yemen

The stimulating herbal drug khat is habitually used in East Africa and the Arabian peninsula but is also imported into other countries. The aim was to study the pharmacokinetics of its alkaloids cathinone, cathine and norephedrine.. Four volunteers chewed khat leaves in an amount equivalent to one-quarter of that used in a typical khat session. Blood samples were collected up to 80 h and the alkaloids were assayed using gas chromatography-mass spectrometry. The data were evaluated using computerized pharmacokinetic compartmental analysis.. The plasma concentration-time data for the alkaloids could be described using a two-compartment model with two-segment absorption. The mucosa of the oral cavity is considered to be the first absorption segment, where the major proportion of the alkaloids is absorbed (mean +/- SD 59 +/- 21% for cathinone and 84 +/- 6% for cathine). The extraction of the alkaloids from the leaves by chewing was very effective with only 9.1 +/- 4.2% remaining as a residue. Cathinone was eliminated from the central compartment with a mean half-life of 1.5 +/- 0.8 h. The half-life of cathine was 5.2 +/- 3.4 h. The metabolism of cathinone to norephedrine had a substantial influence on its plasma concentration profile. Psychophysical functions were essentially unaffected by the chewing of khat.. The pharmacokinetics of khat alkaloids in humans explain why chewing is the preferred form of khat ingestion. Subjects absorbed a mean dose of 45 mg of cathinone, and did not suffer any severe adverse reactions.

Topics: Adult; Alkaloids; Appetite Depressants; Catha; Central Nervous System Stimulants; Female; Humans; Male; Mastication; Middle Aged; Phenylpropanolamine; Plant Leaves

The stimulating herbal drug kath is uncommon in most countries, and information on its detection and interpretation of analytical results is limited. Therefore, a study with kath was carried out to compare the efficiencies of different analytical techniques used to detect drug use.. Four volunteers chewed kath leaves for 1 h; urine samples were collected up to 80 h afterward and analyzed by the Abbott fluorescence polarization immunoassay (FPIA), the Mahsan-AMP(300) on-site immunoassay, the Bio-Rad Remedi HS HPLC system with photodiode array detection (DAD), and gas chromatography-mass spectrometry (GC-MS).. FPIA gave negative results, whereas positive results were obtained with the Mahsan test during the first day. With HPLC, one peak could be observed up to 50 h, but its DAD spectrum could not be identified by the system. Further investigations indicated that the kath alkaloids coeluted and produced a mixed DAD spectrum. With GC-MS, the specific kath ingredient cathinone was detected up to 26 h, whereas cathine and norephedrine were still detectable in the last samples. Maximum concentrations of cathinone, cathine, and norephedrine in urine samples from the study were 2.5, 20, and 30 mg/L, respectively, whereas in authentic cases the concentrations were much higher.. GC-MS is superior to the screening techniques Mahsan-AMP(300) and Remedi with respect to specificity and sensitivity for the detection of kath use in urine.

Topics: Alkaloids; Celastraceae; Chromatography, High Pressure Liquid; Female; Forensic Medicine; Gas Chromatography-Mass Spectrometry; Humans; Immunoassay; Male; Mastication; Phenylpropanolamine; Plant Leaves; Substance Abuse Detection

Like psychomotor stimulants, a weak amphetamine-like agent, such as phenylpropanolamine, enhances the analgesic effects of morphine (MOR). Thus, it is possible that full psychomotor stimulant potency is not required to increase the analgesic action of opiates. The validity of this assumption is here tested by studying the ability of (-)-norpseudoephedrine (NPE), an enantiomer of phenylpropanolamine and a metabolite of cathinone, to influence both the analgesic effects of MOR and its discriminative stimulus properties. In mice NPE (5.6-10.0-17.0 mg/kg i.p.) did not prolong the latency to lick or to remove paws from a plate warmed at 54 degrees C. However, it significantly potentiated the analgesic effect of 3.2 mg/kg of MOR. These results were replicated in rats by use of the formalin test, which measures the numbers of hind paw flinches produced by injecting 50 microl of formalin into the dorsal surface of the paw. The higher dose of NPE (17 mg/kg) increased the effect of sub-analgesic doses of MOR (0.56 and 1.0 mg/kg). In rats trained to discriminate between 0.5 mg/kg of amphetamine and solvent in a two-lever operant behavior reinforced by water access. NPE induced a dose-dependent increment of drug lever responding from 0% at 1.0 mg/kg to 100% at 32.0 mg/kg. In contrast, NPE did not generalize for the MOR cue up to the dose of 56.0 mg/kg, which produced a substantial reduction of the response rate. However, when given in combination, NPE attenuated the discriminative effects of MOR and potentiated its inhibitory action on the response rate. These results exclude a direct action of NPE on the mu opiate system. In conclusion, NPE preserves amphetamine-like properties and these properties are probably responsible for the interaction of the drug with the analgesic and discriminative effects of MOR. Therefore, this study contradicts the assumption that the analgesic effects of MOR can be enhanced by a sympathomimetic drug that lacks significant psychostimulant actions.

Topics: Alkaloids; Amphetamine; Analgesics, Opioid; Animals; Central Nervous System Stimulants; Discrimination, Psychological; Dose-Response Relationship, Drug; Drug Synergism; Female; Formaldehyde; Male; Mice; Morphine; Pain Measurement; Phenylpropanolamine; Rats; Rats, Sprague-Dawley; Reaction Time

The chewing of fresh leaves of the khat bush (Catha edulis) is common in certain countries of East Africa and the Arab peninsula, because this material has a stimulating effect. During the last decade, important progress has been made in understanding the pharmacology of this drug. Its actions are mainly due to the alkaloid cathinone, a substance that can be called 'a natural amphetamine'.

Topics: Alkaloids; Appetite Depressants; Catha; Central Nervous System Stimulants; Humans; Phenylpropanolamine; Plant Extracts

Catha edulis is a plant that grows in certain areas of East Africa and the Arab Peninsula. The stimulating properties of fresh material were described more than seven centuries ago and today the habit of inducing a state of euphoria and subjective well-being by chewing Catha edulis prevails among the inhabitants of these regions. Oral administration of this plant and its active constituents (cathine and cathione) on experimental animals might have stimulating effects on adrenocortical function. This was indicated by the significant decrease in adrenal cholesterol, ascorbic acid, glycogen, and the increase in adrenal phosphorylase activity. In addition, the level of urinary 17-hydroxycorticosteroids and plasma free fatty acids were increased.

Topics: Adrenal Cortex; Alkaloids; Animals; Ascorbic Acid; Catha; Central Nervous System Stimulants; Cholesterol; Fatty Acids, Nonesterified; Male; Phenylpropanolamine; Phosphorylases; Plant Extracts; Rabbits; Steroids

1. Previous studies indicate that rats trained to discriminate either cathinone or cathine from its vehicle have a diminished discriminative performance when tested 24 hours after a drug administration when compared to tests conducted after a vehicle administration. The phenomenon of rapid tolerance may occur to produce a lessened interceptive cue on the test day following administration of the drug. It would, therefore, be probable that when rats are trained with consecutive cathinone or cathine administrations they would perform less well than if they were trained with these drugs never given in consecutive training sessions. 2. To test this hypothesis, rats were trained with 0.8 mg/kg 1-cathinone or 4.8 mg/kg d-cathine in a two-lever, food motivated operant task. Each of these groups were divided into two subgroups with the one receiving consecutive drug administrations and the second never receiving two consecutive administrations of the drug. 3. Results indicate that in the cathine-trained group, there was a significant increase in the time that was necessary to train the animals when consecutive administrations were used in training. This, however, did not occur in the cathinone-treated group. There was, however, no significant difference between the differentially trained groups as to ED50 values. 4. It, thus, appears that there may not be a correlative relationship between speed of acquisition, as documented by sessions-to-criterion, and sensitivity, as indicated by ED50 values.

Topics: Alkaloids; Animals; Appetite Depressants; Central Nervous System Stimulants; Discrimination Learning; Dose-Response Relationship, Drug; Food; Male; Phenylpropanolamine; Psychotropic Drugs; Rats; Rats, Sprague-Dawley; Reinforcement Schedule

A high-performance liquid chromatographic (HPLC) procedure with photodiode-array detection (DAD) is described for the determination of (S)-(-)-cathinone (S-CA) and its metabolites (R,S)-(-)-norephedrine (R-NE) and (R,R)-(-)-norpseudoephedrine (R-NPE) in urine. Extraction and clean-up of 1-ml urine samples were performed on a cyano-bonded solid-phase column using (+/-)-amphetamine as internal standard. The concentrated extracts were separated on a 3-microns ODS-1 column with acetonitrile-water-phosphoric acid-hexylamine as the mobile phase. Peak detection was done at 192 nm. The detection limits for S-CA and R-NE/R-NPE in urine were 50 and 25 ng/ml, respectively. The differentiation of the enantiomers of cathinone and norephedrine was achieved by derivatization with (S)-(-)-1-phenylethyl isocyanate to the corresponding diastereomers followed by HPLC-DAD on a 5-microns normal-phase column. The R and S enantiomers of norpseudoephedrine were determined by gas chromatography-mass spectrometry after on-column derivatization with (S)-(-)-N-trifluoroacetylprolyl chloride. Following a single oral dose of 0.5 mg/kg of S-CA, the concentrations found in urine ranged from 0.2 to 3.8 micrograms/ml of S-CA, from 7.2 to 46.0 micrograms/ml of R-NE and from 0.5 to 2.5 micrograms/ml of R-NPE.

Topics: Alkaloids; Chromatography, High Pressure Liquid; Humans; Phenylpropanolamine; Psychotropic Drugs; Reproducibility of Results; Spectrophotometry, Ultraviolet; Stereoisomerism

The drug discrimination paradigm was used to evaluate in rats the ability of the discriminate response to either 0.8 mg/kg d-amphetamine or 0.8 mg/kg l-cathinone to generalize to 2.4-6.0 mg/kg of the active cathinone metabolite d-norpseudoephedrine, also known as cathine. When tested 24 h after vehicle administration, cathine generalized in a dose-related fashion in rats (n = 6) trained with cathinone (ED50 = 3.03 mg/kg) and in rats (n = 8) trained with amphetamine (ED50 = 2.93 mg/kg). In contrast, when cathine was tested 24 h after the administration of either amphetamine or cathinone, it produced significantly decreased discriminative performance. The possibility that this acute tolerance may have been produced by release, and subsequent depletion, of brain dopamine was tested by pretreating rats with the dopamine release inhibitor CGS 10746B. When CGS 10746B was administered prior to cathinone it significantly decreased cathinone discrimination. In addition, acute tolerance to cathine at 24 h after vehicle-cathinone co-administration was reversed when cathine was tested 24 h after CGS 10746B-cathinone co-administration. The results suggest that cathinone-produced discriminative stimulus, as well as the acute tolerance to cathine, may be dopaminergically mediated.

Topics: Alkaloids; Amphetamine; Animals; Antipsychotic Agents; Discrimination, Psychological; Dose-Response Relationship, Drug; Drug Tolerance; Male; Phenylpropanolamine; Psychotropic Drugs; Rats; Rats, Inbred Strains; Thiazepines

Cathine is a psychoactive constituent in the leaves of the Khat shrub which are habitually ingested for their stimulatory effects in many parts of the world. Rats were trained to discriminate the stimulus effect of intraperitoneally administered 4.8 mg/kg d-cathine and, once trained, administration of another Khat constituent, cathinone, was shown to produce cathine-like effects. This generalization to cathinone was dose-responsive when testing occurred 24 hr after vehicle administration, whereas prior administration of cathine resulted in a diminished discriminative response to subsequent cathinone administration possibly as a result of the development of acute tolerance. CGS 10746B, a compound that blocks presynaptic release of dopamine, significantly decreased rats' ability to discriminate cathine when it was administered 25 min prior to cathine testing and it reversed the acute tolerance observed when cathine was tested 24 hr after cathine administration. These results indicate that a previously reported acute tolerance effect to cathine after cathinone administration in cathinone-trained rats appears to be symmetrical in that there is acute tolerance to cathinone after cathine in these cathine-trained rats. The results with CGS 10746B would suggest that both the cathine-induced discriminative cue and cathine's ability to produce acute tolerance are mediated by presynaptic dopamine release.

Topics: Alkaloids; Animals; Antipsychotic Agents; Appetite Depressants; Discrimination Learning; Discrimination, Psychological; Dopamine; Dose-Response Relationship, Drug; Drug Tolerance; Generalization, Psychological; Male; Phenylpropanolamine; Rats; Rats, Inbred Strains; Thiazepines

The CNS-stimulating properties of leaves of the khat shrub (Catha edulis, Celastraceae) are presumed to be due mainly to (-)-cathinone, a phenylpropylamine alkaloid that has been shown to have an amphetamine-like releasing effect at physiological catecholamine storage sites. Recently, several phenylpentenylamine alkaloids have been identified in khat leaves, and these have been evaluated, in-vitro, in the present study for their ability to induce release of radioactivity from [3H]dopamine-prelabelled rat striatal tissue. It was found that the phenylpentenylamines have a weak releasing effect, and are therefore considered unlikely to play an important role in the stimulating properties of khat leaves.

Topics: Alkaloids; Amines; Animals; Catha; Caudate Nucleus; Central Nervous System Stimulants; Dopamine; In Vitro Techniques; Phenylpropanolamine; Plant Extracts; Rats; Tritium

Topics: Alkaloids; Humans; Phenylpropanolamine; Plants; Substance-Related Disorders; United Kingdom

(-)-Cathinone and d-norpseudoephedrine (DNE) in the dose range 0.2-1.2 mg/ml produced a reduction in contractions of skeletal muscle, evoked by direct and indirect electrical stimulation and antagonised the facilitatory action of physostigmine on the neuromuscular junction; but failed to antagonise a partial blockade induced by d-tubocurarine (dTb) as occurs with norepinephrine or epinephrine. The local anaesthetic actions of (-)-cathinone and DNE were found to be almost equivalent to that of lignocaine. These results indicate that (-)-cathinone and DNE may have a direct blocking action on the neuromuscular junction, which is independent of cholinergic and adrenergic transmission.

Topics: Alkaloids; Animals; Epinephrine; Lidocaine; Neuromuscular Junction; Norepinephrine; Phenylpropanolamine; Physostigmine; Rats; Synaptic Transmission; Tubocurarine

Khat, the leaves of Catha edulis Forsk. (Celastraceae), is widely used as a stimulant in East Africa and the Arab Peninsula. Samples from the most important markets of Ethiopia, Kenya, North Yemen and Madagascar were analysed with high-performance liquid chromatography (HPLC) concerning their khatamine content (phenylpropyl and phenylpentenylamines). The variability of khatamines depending on origin, type and quality is discussed. In many samples a good correlation between the amount of cathinone, the main CNS-active compound, and quality estimation (price) of dealers and consumers was found.

Topics: Africa, Eastern; Alkaloids; Amphetamine; Asia, Western; Catha; Chromatography, High Pressure Liquid; Phenylpropanolamine; Plant Extracts; Plants, Medicinal; Psychotropic Drugs

In order to analyse further the discriminative stimulus properties of stimulant drugs, rats were trained to discriminate 2.0 mg/kg of dl-cathinone in a two-lever operant task. Dose-related generalization was seen to cathinone itself and to a wide range of stimulant drugs including d-amphetamine, cocaine, methylphenidate, pipradrol and cathine, i.e. (+)norpseudoephedrine. The high degree of specificity of the cathinone cue at the specific training dose studied was shown by the fact that the following nonstimulant drugs failed to generalize at all to cathinone, even in large doses--haloperidol, chlordiazepoxide, fenfluramine and fentanyl. The cathinone cue at 2.0 mg/kg was probably of central origin because phydroxyamphetamine (a polar congener of amphetamine) failed to generalize to cathinone at a dose nearly 50 times the ED50 for amphetamine generalization. Phenylethylamine (PEA; alpha-demethylamphetamine) and deuterated phenylethylamine (alpha, alpha, d2-PEA), a long acting derivative of phenylethylamine which is resistant to metabolism by monoamine oxidase, produced at most partial (60%) generalization to cathinone, even in large doses. alpha-Demethylcathinone failed to generalize at all to cathinone at doses up to 10 times the ED50 for cathinone. Thus, the alpha-methyl groups of both amphetamine and cathinone are important in determining their cue properties. The involvement of dopaminergic systems in the cathinone cue was investigated by examining generalization to apomorphine and antagonism by haloperidol. Apomorphine produced at most 29% generalization to cathinone. Haloperidol, at doses up to 0.3 mg/kg, produced at most 50% antagonism of both the cathinone cue and of the ability of amphetamine to substitute for cathinone. It is suggested that the evidence for dopaminergic mediation of the cue properties of cathinone and of other CNS stimulants is somewhat tenuous, whilst endogenous phenylethylamine may play some part in the mediation of the stimulant cue. Haloperidol, alone and in conjunction with amphetamine or cathinone, produced a remarkable tendency for subjects to emit a greater proportion of their total responses on the inoperative rather than the operative lever than was seen after saline or injections of vehicle. This action of a neuroleptic drug suggests, in accordance with Colpaert, Niemegeers and Janssen (1977), that in drug discrimination antagonism studies involving neuroleptics, and perhaps other drugs, quantal (lever selection) rathe

Topics: Alkaloids; Animals; Brain; Central Nervous System Stimulants; Cocaine; Conditioning, Operant; Cues; Dextroamphetamine; Discrimination Learning; Female; Generalization, Stimulus; Methylphenidate; Phenylpropanolamine; Piperidines; Rats

S-(-)-Cathinone (S-(-)-alpha-aminopropiophenone) is the major active principle of khat leaves (Catha edulis), which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. After oral administration of synthesized cathinone (isomers, racemate), 22-52% was recovered in 24 h urine samples mainly as aminoalcohol metabolites. With GC/MS, HPLC and CD, the main metabolite of S-(-)-cathinone was identified as R/S-(-)-norephedrine and the main metabolite of R-(+)-cathinone as R/R-(-)-norpseudoephedrine. Both aminoalcohols are formed by a stereospecific keto reduction.

Topics: Alkaloids; Biotransformation; Chromatography, High Pressure Liquid; Circular Dichroism; Gas Chromatography-Mass Spectrometry; Humans; Male; Phenylpropanolamine; Stereoisomerism

Rats trained to discriminate between the stimulus properties of 0.6 mg/kg of racemic cathinone and its vehicle, in a two-lever operant task for food reinforcement, were administered doses of S(-)-cathinone, R(+)-cathinone, (+)-cathine and several structurally-related derivatives, in order to study structure-activity relationships. The optical isomers of cathinone and (+)-cathine produced patterns of responding similar to that observed with the training drug; S(-)-cathinone (ED50 = 0.22 mg/kg) was the more active of the two isomers, while R(+)-cathinone (ED50 = 0.72 mg/kg) was more active than (+)-cathine (ED50 = 1.61 mg/kg). In contrast, removal of the alpha-methyl group of cathinone, or substitution at the 4-position of racemic cathinone by a hydroxyl, methoxyl or chloro group, essentially abolished activity at dose levels comparable to the training dose of cathinone.

Topics: Alkaloids; Animals; Behavior, Animal; Discrimination, Psychological; Male; Phenylpropanolamine; Rats; Rats, Inbred Strains; Reinforcement Schedule; Stereoisomerism; Structure-Activity Relationship

Kat is being used extensively in many countries as a central nervous system stimulant. The effect of three doses of crude kat extract on chromosomal division and abnormalities in bone marrow, as well as on DNA, RNA, and total protein content in brain and liver was studied in laboratory rats in order to test the possible mutagenicity of the drug. Kat was given as a single subcutaneous injection at 0.05 (usage dose), 0.52 (intermediate dose), and 1.00 (sublethal dose) g/kg body weight. Animals were sacrificed at 6, 24, and 48 hr after treatment. Also, some animals were exposed subacutely for 5 consecutive days with sacrifice occurring 6 hr after the last injection. The mitotic index was reduced by all treatments, with the greatest effect occurring in the subacute treatment. Chromosomal abnormalities were induced by kat at all three doses, administered acutely or subacutely. The significant chromosomal aberrations were in the form of gaps, breaks, centromeric attenuations, and centric fusions. The concentration of DNA, RNA, and total protein in liver and brain decreased at all doses, with the greatest decrease occurring after subacute treatment. These findings suggest that kat has a profound effect on cell proliferation, on chromosomal abnormalities, and on DNA, RNA, and total protein synthesis.

Topics: Alkaloids; Animals; Bone Marrow; Brain; Catha; Chromosome Aberrations; Liver; Male; Mitosis; Nucleic Acids; Phenylpropanolamine; Plant Extracts; Proteins; Rats

Consumption of khat leaves produces symptoms that are similar to those caused by amphetamine. The experiments reported in the following describe the effect of the two khat alkaloids (-)-cathinone and (+)-norpseudoephedrine at the cellular level. Both were shown to induce release from physiological catecholamine storage sites. Peripheral noradrenaline sites (rabbit heart) were observed to be more sensitive than CNS dopamine sites (rat nucleus accumbens). In the latter organ, which is believed to be involved in amphetamine hypermotility, (-)-cathinone was considerably more potent than (+)-norpseudoephedrine.

Topics: Alkaloids; Animals; Catecholamines; Dopamine; In Vitro Techniques; Myocardium; Nucleus Accumbens; Phenylpropanolamine; Rabbits; Rats

Cathinone, a potent psychostimulant isolated from young shoots of Catha edulis was given to four human volunteers. Examination of urine collected from the volunteers at predetermined intervals showed the presence of unchanged cathinone, d-norpseudoephedrine, and two unidentified basic substances. The observed biotransformation of cathinone to the less potent psychostimulant, d-norpseudoephedrine involves reduction of a ketone group to alcohol, a common metabolic pathway in humans.

Topics: Alkaloids; Biotransformation; Chromatography, Thin Layer; Humans; Kinetics; Phenylpropanolamine

Topics: Alkaloids; Catha; Kenya; Phenylpropanolamine; Plant Extracts

Topics: Alkaloids; Amphetamines; Animals; Behavior, Animal; Brain Chemistry; Corpus Striatum; Dopamine; Female; Male; Phenylpropanolamine; Rats

Topics: Alkaloids; Animals; Central Nervous System Stimulants; Conditioning, Operant; Dose-Response Relationship, Drug; Humans; Male; Phenylpropanolamine; Plants, Medicinal; Propiophenones; Rats; Substance-Related Disorders; Time Factors

The effect of khat (Catha edulis Forsk., family Celastraceae), a plant used for its stimulant effects in eastern Africa and southern Arabia, has until recently been attributed to the pharmacological action of d-norpseudoephedrine, also known as cathine. The isolation in 1975 of cathinone revived an earlier suggestion that the fresh leaves contained a substance more potent than cathine. The pharmacological assays reported on in this paper appear to confirm the higher stimulant capacity of cathinone. This substance produces qualitatively similar locomotor stimulation in mice and comparable stereotypy in rats as amphetamine does, although it is approximately half as active. The results obtained after pre-treatment with reserpine or alpha-methyl-p-tyrosine, which interfere with the catecholamine system, strongly suggest that cathinone interacts with brain catecholamines by an indirect mechanism and, most probably, by affecting neurotransmitter release of the labile pool.

Topics: Alkaloids; Amphetamine; Animals; Apomorphine; Appetite Depressants; Catecholamines; Catha; Haloperidol; Humans; Male; Mice; Motor Activity; Nomifensine; Phenylpropanolamine; Plant Extracts; Rats; Reserpine; Stereotyped Behavior

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

Topics: Alkaloids; Phenylpropanolamine; Plants; Propiophenones

Topics: Alkaloids; Amphetamine; Animals; Cats; Guinea Pigs; Mice; Phenylpropanolamine; Propiophenones; Rabbits; Rats; Sympathetic Nervous System