Evaluation of a cooperative group human myeloma protocol using the MOPC 104E myeloma model.
Data are presented on the response rates, maximum rate of cell kill, and survival rates for individual and groups of mice with MOPC 104E myeloma treated with a variety of chemotherapeutic agents and combination regimens used in clinical human myeloma. The tumor immunoglobulin M measurements are used to evalutae the therapeutic effects of drugs. Prednisolone and mescaline, when given as single drugs, showed no therapeutic action and the animals died of tumor as in the controls. The immunoglobulin M values are very similar and ranged between 8,125 and 13,410 mug/mouse. Prednisolone and melphalan given in combination indicated therapeutic effect. 1,3-Bis(2-chloroethyl)-1-nitrosourea-cyclophosphamide-prednisolone combination caused tumor regression but was toxic as shown by the immunoglobulin M values and percentage of survival. The complications and potential uses of this system, which utilized only 40 animals in 64 days, are discussed. (+info)
A comparison of the effect of mescaline on activity and emotional defaecation in seven strains of mice.
1 Mescaline hemi-sulphate (35 mg/kg body weight) was injected intraperitoneally into male mice (Mus musculus) from seven genetically diverse laboratory strains. 2 The effect of mescaline was found by comparison of the emotional defaecation and open field activity of mice after mescaline injection with the performance of the same mice after a subsequent saline (0.9% w/v NaCl solution) control injection. 3 In strains A2G, C3H/He, C57BR/cd, CBA/Cam and F/St, mescaline inhibited emotional defaecation and stimulated open field activity. These effects did not occur in strains 1CFW and Schneider. 4 A positive relationship was found between the degree of emotional defaecation characteristic of each strain in the saline control experiment and the inhibitory effect of mescaline on emotional defaecation. 5 Pre-treatment of mice with tranylcypromine (20 mg/kg body weight, i.p.) had no effect on emotional defaecation or on its inhibition by mescaline. (+info)
Potentiation by desipramine of neuronal responses to mescaline.
The effect of desipramine on responses of single cortical neurones to mescaline was studied by the microelectrophoretic technique. Both potentiation and antagonism of responses to mescaline by desipramine were observed. The antagonism may be related to the alpha-adrenolytic action of desipramine. The potentiation is unlikely to reflect the uptake blocking action of desipramine, since desipramine does not block the uptake of mescaline in the cerebral cortex. It is suggested that the potentiation may be due to a post-synaptic action of desipramine. (+info)
SCIENCE, MYSTICISM AND PSYCHOPHARMACOLOGY.
Historically, psychopharmaceutical agents have been used to produce a mystical state with the religious connotation of "a union with Divine Nature" or of "oneness with God." Such transcendental states are also known to occur in starvation, self-flagellation, Yoga and various psychoses.A common psychological origin is suggested for these states, in which there is a psychic regression to an early phase of development. This genetically is the phase wherein the infant is still united with the mother and has not yet established the boundaries between the "self" and the "not-self." In a subtler form, the desire to regress to this phase may be a universal yearning which affects the physician, the investigator and even the manufacturer of drugs. Accordingly, we have a profusion of tranquilizers, euphoriants and ataractics the prescription or the investigation of which may give vicarious pleasure and relief of tension to the physician and scientist by a process of identification with the person receiving the drug.Mankind's quest for psychic development is difficult and precarious, alternately marked by progression and regression. Excesses in the use of drugs are indicated as regressive in nature. (+info)
Nootropic candidates inhibit head-twitches induced by mescaline in mice.
The effects of various nootropic candidates on mescaline-induced head-twitches were studied in mice. The number of head-twitches induced by mescaline (100 mg/kg, s.c.) was significantly reduced by idebenone (32 and 100 mg/kg, i.p.), minaprine (0.32-10 mg/kg, p.o.) and nebracetam (100 mg/kg, p.o.). Cholinesterase inhibitors such as tetrahydroaminoacridine (1 and 10 mg/kg, p.o.), NIK-247 (10 and 18 mg/kg, p.o.) and physostigmine (0.32 mg/kg, i.p.) also suppressed the head-twitch response to mescaline. These results suggest that the direct or indirect cholinergic-activating effects of these drugs may be involved in inhibiting mescaline-induced head-twitches. (+info)
The analysis and distribution of mescaline in postmortem tissues.
Mescaline (3,4,5-trimethoxyphenethylamine) is a hallucinogenic alkaloid found in the peyote cactus. This report documents mescaline distribution in a death caused by multiple gunshot wounds. Mescaline was extracted with a butyl chloride liquid-liquid method and identified by mass spectrometry. Quantitative analysis was performed by gas chromatography using a nitrogen-phosphorus detector. Concentrations of the drug were 2.95 mg/L, 2.36 mg/L, 8.2 mg/kg, and 2.2 mg/kg in blood, vitreous, liver, and brain, respectively. (+info)
Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors.
2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5-hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.g., phospholipase A(2) (PLA(2))] are associated with these receptors. We compared two homologous series of phenylisopropylamines and phenethylamines measuring both PLA(2) and PLC responses in Chinese hamster ovary-K1 cells expressing human 5-HT(2A) or 5-HT(2C) receptors. In addition, we assayed both groups of compounds as head shake inducers in rats. At the 5-HT(2C) receptor, most compounds were partial agonists for both pathways. Relative efficacy of some phenylisopropylamines was higher for both responses compared with their phenethylamine counterparts, whereas for others, no differences were found. At the 5-HT(2A) receptor, most compounds behaved as partial agonists, but unlike findings at 5-HT(2C) receptors, all phenylisopropylamines were more efficacious than their phenethylamine counterparts. 2,5-Dimethoxyphenylisopropylamine activated only the PLC pathway at both receptor subtypes, 2,5-dimethoxyphenethylamine was selective for PLC at the 5-HT(2C) receptor, and 2,5-dimethoxy-4-nitrophenethylamine was PLA(2)-specific at the 5-HT(2A) receptor. For both receptors, the rank order of efficacy of compounds differed depending upon which response was measured. The phenylisopropylamines were strong head shake inducers, whereas their phenethylamine congeners were not, in agreement with in vitro results and the involvement of 5-HT(2A) receptors in the head shake response. Our results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile. (+info)
Development and clinical application of an LC-MS-MS method for mescaline in urine.
Mescaline (3,4,5-trimethoxyphenylethylamine) is an hallucinogenic psychoactive substance present in several species of cacti. Mescaline has a documented use dating back 5700 years. In more recent years, the interest in hallucinogenic designer drugs such as ecstasy has also triggered interest in the naturally occurring mescaline. This study was undertaken to develop a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the screening and confirmation of mescaline in human urine samples and to apply this method to routine testing in patient samples. For the screening procedure, chromatographic separation was achieved on a 5-microm HyPURITY C(18) column, using a methanol gradient in ammonium acetate buffer. The MS-MS analysis was performed using selected reaction monitoring; the transitions monitored were m/z 212.3 --> m/z 180.3 for mescaline and m/z 221.3 --> m/z 186.3 for the deuterated internal standard (mescaline-d(9)). The detection limit for mescaline in urine matrix was 3-5 microg/L, the upper limit of quantification was 10,000 microg/L, and the total coefficient of variation for spiked samples containing 10 to 1025 microg/L was < 8.5%. The confirmation procedure included a sample clean-up by solid-phase extraction on a C(18) cartridge, and one extra transition for mescaline (m/z 212.3 --> m/z 195.2) was monitored. The LC-MS-MS method was found to be sensitive and specific for the routine detection of mescaline in urine. Among 462 urine samples collected from young people with alcohol or drug problems, 32% were positive for illicit drugs, but none for mescaline. (+info)