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PubMed1975

A crystallographic and theoretical study of the conformation of DOET and its significance for the hallucinogenic amphetamines.

The crystal and molecular structure of 2, 5-dimethoxy-4-ethyl-alpha-methyl-phenylethylamine (DOET) has been determined by X-ray crystallography and the conformation of the side chain has been examined theoretically by the use of a potential energy calculation. There is no indication in the solid state of any intra or inter-molecular hydrogen bonding. The isopropylamine side chain is staggered to the plane of the benzene ring. The alpha-methyl group is fully extended (antiplanar) whereas the amino group is orientated back towards the ring (synclinal). The potential energy calculations show the existence of 6 minima, one of which corresponds to the crystal position. The calculations also show that the energy differences between the various minima of the side chain are very small. The relationship of these data to the conformations of the hallucinogens, mescaline and 2, 4, 5,-trimethoxyamphetamine is discussed.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1978

[Psychopharmacological effects of flutazolam (MS-4101) (author's transl)].

Behavioral effects of Flutazolam (MS-4101), a new derivative of benzodiazepines, was investigated and compared with effects of diazepam in mice and rats. MS-4101 suppressed hyperemotionality in septal rats, fighting behavior in long-term isolated mice and pentylenetetrazol convulsion and potentiated thiopental sleep. These effects of MS-4101 were the same in potency as those of diazepam. MS-4101 was more potent than diazepam in reducing the spontaneous locomotor activity in the open-field test and potentiating the stimulant effect of methamphetamine on locomotor activity. On the other hand, suppression of hyperemotionality in O. B. rats, potentiation of ethanol-induced anesthesia, prevention of maximal electroshock, prevention of strychnine convulsin and muscle relaxant effect of MS-4101 were less potent than in the case of diazepam. MS-4101 had also an anticonflict effect, which was less potent than that seen with diazepam. Suppression of locomotor activity was potentiated by chronic administration of MS-4101, but disappeared with chronic administration of diazepam. MS-4101 inhibited considerably both scratching and head-twitch induced by mescaline in mice. Scratching was increased with small doses of diazepam and decreased with high doses. Head-twitch was decreased with small doses of diazepam and increased with high doses.

Agonistic Behavior↗
PubMed1975

Some correlates of drug use among high school youth in a Midwestern rural community.

A study of the correlates of drug use (marijuana, LSD, mescaline, speed) among high school youth in a rural, Midwestern community indicated that peer group factors were the most influential in such behavior. Also, youth from less intact families and whose parents were perceived to use various legal drugs were more prone to drug use. Drug education was seen as not having as significant an impact in differentiating between users and nonusers nor in deterring users from further involvement. In support of previous research, we conclude that drug use is a form of behavior learned through peer and family socialization.

Adolescent↗
PubMed1977

Peyote, a potential ethnopharmacologic agent for alcoholism and other drug dependencies: possible biochemical rationale.

The authors examine folk psychiatry among Native American Church members from an enthnopharmacologic viewpoint. Alcohol and opiate abuse among Indian and non-Indian are presented in case histories proving to be asymptomatic under Indian guidance and through participation in the peyote ritual. The biochemical alkaloids common in the peyote cactus, rather than just the psychoactive substances (mescaline), are purported to be pharmacologically similar to the neuroamine-derived alkaloids found in the brain during alcohol intoxification. Evidence is reviewed that points out possible common features of alcohol and opiate dependence leading to the speculation for a common mode of treatment may reside in plants rich in isoquinoline alkaloids.

Adult↗
PubMed1975

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.

Animals↗
PubMed2001

Peyote use during pregnancy.

Peyote is a substance with varied potential. Used properly it may be a spiritual aid but used in excess, it can be a hallucinogenic agent with teratogenic potential. There is a growing community of devout people who use it as part of their religious observance. The active ingredient, mescaline, has been linked to a specific group of fetal abnormalities when the substance is used inappropriately.

Abnormalities, Drug-Induced↗
PubMed1975

Effect of peyote on human chromosomes. Cytogenetic study of the Huichol Indians of Northern Mexico.

Fify-seven Huichol Indians with a lifelong individual history and a 1,600-year cultural tradition of ingestion of peyote, a mescaline-containing cactus possessing hallucinogenic properties, were compared with 50 Huichol Indian controls and ten laboratory controls for effects on lymphocyte chromosomes. The frequency of abnormalities in the experimental and control groups did not differ significantly. Our results indicate that multigenerational ingestion of peyote is not associated with abnormalities in lymphocyte chromosomes.

Adolescent↗
PubMed1975

On the role of catecholamines in the humoral modulation of the electrocortical activity in the cat.

By using the mescaline or the strychnine spikes as indicators of electrocortical activity it was found that they are increased in size by some catecholamines topically applied. These spikes showed late and long-lasting changes after somatic, as well as after autonomic afferent stimulation. The latter induced by cyanide, light asphyxia, intravenous injections of adrenaline or noradrenaline, and after a small dose of 6-hydroxydopamine. After a dose of this last substance, high enough to deplete the catecholamines of the brain, the late increase in amplitude of the cortical potentials observed following afferent stimulation disappeared leaving a long lasting reduction in that amplitude. The hypothesis is presented that the noradrenaline liberated by the adrenergic nerve fibers reaching the upper layers of the cortex acts on the nonsynaptic dendritic membranes modulating their activity in a humoral-like way. The pattern of this facilitating effect has a different temporal course and is longer lasting than that which is to be expectec only by the arrival of impulses at the cortex during the persistence of the neuronal activation induced by the information input to the CNS.

Animals↗
PubMed1992

DuP 734 [1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)-2'- oxoethyl)piperidine HBr], a potential antipsychotic agent: preclinical behavioral effects.

It has been suggested that sigma receptors may be involved in the etiology of psychosis and that 5-hydroxytryptamine2 (5-HT2) antagonists may have utility in treating the negative symptoms of psychosis as well as reducing the side effects associated with the typical antipsychotic haloperidol. We have evaluated the potential antipsychotic effects of 1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)-2'-oxoethyl)piper i din e HBr (DuP 734), a selective and potent sigma and 5-HT2 receptor ligand with weak affinity for D2 receptors, in behavioral animal models that are not necessarily dependent on dopamine antagonism. DuP 734 potently blocked mescaline-induced scratching (ED50 = 0.35 mg/kg, p.o.) and aggressive activity (ED50 = 1.9 mg/kg, p.o.) and was relatively much weaker as an apomorphine antagonist (ED50 = 12 mg/kg, p.o.). This was in contrast to the typical antipsychotic agents such as haloperidol and chlorpromazine, which were very potent in all three tests. In rats, DuP 734 did not antagonize avoidance behavior or induce catalepsy, and, therefore, differed from the potent dopamine receptor antagonist antipsychotics. It did, however, reduce lever response rates in a random interval 60-sec food reward schedule of reinforcement (ED50 = 6.0 mg/kg, p.o.) in rats. The results suggest that DuP 734 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics. Although DuP 734 itself did not antagonize avoidance activity, it significantly enhanced the potency of haloperidol in blocking avoidance behavior by 3-fold (by shifting the ED50 from 0.94 to 0.36 mg/kg, p.o.), whereas the ED50 of haloperidol for blockade of escape behavior and induction of catalepsy was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗
PubMed1990

Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain.

A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a decrease in serotonin2 (5-hydroxytryptamine2, 5-HT2) binding in cortex (measured 24 hours after the last drug administration) but did not affect binding to other receptor systems (5-HT1A, 5-HT1B, beta-adrenergic, alpha 1- or alpha 2-adrenergic, D2-dopaminergic) or to a recognition site for 5-HT uptake. The decrease was evident within 3 days of LSD administration but was not demonstrable after the first LSD dose. Following 5 days of LSD administration the decrease was still present 48 hours, but not 96 hours, after the last administration. The indole hallucinogen psilocybin [1.0 mg/kg (3.5 mumol/kg) for 8 days] also produced a significant decrease in 5HT2 binding, but neither the nonhallucinogenic analog bromo-LSD [1.3 mg/kg (2.4 mumol/kg) for 5 days] nor mescaline [10 mg/kg (40.3 mumol/kg) for 5 or 10 days] affected 5-HT2 binding. These observations suggest that LSD and other indole hallucinogens may act as 5-HT2 agonists at postsynaptic 5-HT2 receptors. Decreased 5-HT2 binding strikingly parallels the development and loss of behavioral tolerance seen with repeated LSD administration, but the decreased binding per se cannot explain the gamut of behavioral tolerance and cross-tolerance phenomena among the indole and phenylethylamine hallucinogens.

Animals↗
PubMed1991

Substance abuse: the designer drugs.

Designer drugs, chemically altered compounds derived from federally controlled substances, have become a major cause of addiction and overdose deaths. These drugs include mescaline analogs, synthetic opioids, arylhexylamines, methaqualone derivatives and crack, a new form of cocaine. Sudden changes in mood, weight loss, depression, disturbed sleep patterns, deteriorating school or work performance, marital problems, and loss of interest in friends and social activities may be signs of drug addiction. Life-threatening complications of acute intoxication, such as hyperthermia, seizures, combative and psychotic behavior, and cardiorespiratory collapse, require prompt diagnosis and supportive intervention.

Clinical Protocols↗
PubMed1978

[Effect of psychotomimetics and haloperidol on head twitching following alcohol withdrawal in mice].

After ethanol withdrawal dependent mice exhibited head twitching. The frequency of head-twitches was decreased by LSD and mescaline in a dose-dependent manner and increased by small doses of haloperidol and physostigmine. LSD antagonized the potentiating effects of haloperidol and physostigmine. The incidence of head-twitches after intracerebral injections of 5-HT in naive mice was lessened by LSD. The involvement of dopaminergic, serotoninergic, and cholinergic transmission systems in the action of psychotomimetics is discussed.

Animals↗
PubMed1976

Drugs and PGO waves in the lateral geniculate body of the curarized cat. V. Miscellaneous compounds. Synopsis of the role of central neurotransmitters on PGO wave activity.

In the last part of this series we have studied the effects of various drugs on ponto-geniculo-occipital (PGO) waves induced by the benzoquinolizine derivative, Ro 4-1284 (PGO(1284)), and by the inhibitor of trypotophan hydroxylase, p-chlorophenylalanine (PGO(PCPA)), and continuously recorder and counted in the lateral geniculate bodies (LGB) of unanaesthetized and immobilizedcats. The major aim of this study was to test the specificity of drug-induced alterations of the PGO wave activity suggested by the previous investigations. Hypnotics-sedatives of different classes had no significant effects in doses that did not markedly alter the electrical background activity in the LGB. A notable exception was gamma-hydroxybutyric acid which increased the density of PGO(1284) and PGO(PCPA). A number of neuroleptics were found inactive; sulpiride surprisingly decreased the density of PGO(1284). Bulbocapnine had a similar effect. Convulsants in subconvulsive doses did not uniformly affect PGO waves; while pentetrazole had no consistent effect, strychnine decreased and picrotoxin increased the density of PGO(1284). High doses of morphine, methadone and meperidine decreased the PGO(1284). Ethanol was inactive even in high doses. Caffeine and mefexamide reduced the density of PGO(1284). Mepiprazol was the most potent depressant of PGO(1284, probably by inhibiting the uptake of 5-HT. Mescaline was a weak depressor of PGO(1284). p-Chloromethamphetamine induced PGO waves in untreated cats less consitently than did PCPA. Amantadine reduced the amplitude of PGO waves due to a central antinicotinic action. The results of this study and of the whole series suggested a tentative scheme of the generation and modulation of PGO waves, in which the hypothetical roles and sites of action of four central neurotransmitters are included.

Amantadine↗
PubMed1981

Methylenedioxyamphetamine. Clinical description of overdose, death, and review of pharmacology.

Methylenedioxyamphetamine is a commonly used "street drug", with a reputation of providing a "good trip". The drug is structurally similar to both mescaline and amphetamine. The following symptoms were found in a patient: sympathomimetic effects, coma, seizures, hyperreflexia, and hyperthermia. The patient's condition was initially stabilized and then deteriorated with uncontrollable hyperthermia, hematologic abnormalities, and coma that culminated in death. Since the hyperthermia is based on both central and peripheral mechanisms, phentolamine (Regitine) mesylate may be the preferred drug to be used in the treatment of future cases. The concept that this drug is primarily a hallucinogen with mild toxicity is erroneous.

3,4-Methylenedioxyamphetamine↗
PubMedDate not supplied

Application of a radioimmunoassay screening test for detection and management of phencyclidine intoxication.

A radioimmunoassay procedure has been developed to monitor patients suspected of phencyclidine (PCP) intoxication. Symptoms in 11 patients suspected of phencyclidine intoxication included violent, aggressive behavior with delusions, hallucinations, agitation, and other signs of toxic psychosis. In five subjects serum concentrations of PCP ranged between 0.5 and 40 ng/ml. For laboratory confirmation, ascorbic acid should be administered to the patient after collecting the initial urine specimen. The initial urine and the first and second specimen after acidification should be collected and submitted for analysis. By following this provocative mobilization procedure, phencyclidine has been identified in the first or second postacidification urine when the initial specimen gave either a negative or questionable reaction. Patients reporting to emergency rooms with hallucinations and psychosis and a history of "pot" smoking should be screened for the presence of phencyclidine in their blood and urine. For those cases that turn out to be negative for the phencyclidine group of compounds, other hallucinogenic drugs such as lysergic acid diethylamide, ketamine, mescaline, or psilocybin may be suspect.

Adolescent↗
PubMed1976

Sulfur analogs of psychotomimetic amines.

The syntheses and physical properties are described for 2,5-dimethoxy-4-methylthiophenylethylamine and 2,5-dimethoxy-4-methylthiophenylisopropylamine. The latter compound is the sulfur analog of the psychotomimetic phenylisopropylamines 2,4,5-trimethoxyphenylisopropylamine and 2,5-dimethoxy-4-methylphenylisopropylamine wherein the methylthio group replaces a methoxy group or a methyl group, respectively. This compound is predicted to be about 30 times as active as mescaline.

Hallucinogens↗
PubMed2004

Activation of 5-HT2 receptors enhances the release of acetylcholine in the prefrontal cortex and hippocampus of the rat.

The role of 5-HT2 receptors in the regulation of acetylcholine (ACh) release was examined in the medial prefrontal cortex and dorsal hippocampus using in vivo microdialysis. The 5-HT(2A/2C) agonist +/-1-(2,5-dimethoxy-4-iodophenyl) -2- aminopropane hydrochloride (DOI) (1 and 2 mg/kg, i.p.) significantly increased the extracellular concentration of ACh in both brain regions, and this response was attenuated in rats treated with the 5-HT(2A/2B/2C) antagonist LY-53,857 (3 mg/kg, i.p.). Treatment with LY-53,857 alone did not significantly alter ACh release in either brain region The 5-HT(2C) agonist 6-chloro-2-(1-piperazinyl)-pyrazine) (MK-212) (5 mg/kg, i.p.) significantly enhanced the release of ACh in both the prefrontal cortex and hippocampus, whereas the 5-HT2 agonist mescaline (10 mg/kg, i.p.) produced a 2-fold increase in ACh release only in the prefrontal cortex. Intracortical, but not intrahippocampal, infusion of DOI (100 microM) significantly enhanced the release of ACh, and intracortical infusion of LY-53,857 (100 microM) significantly attenuated this response. These results suggest that the release of ACh in the prefrontal cortex and hippocampus is influenced by 5-HT2 receptor mechanisms. The increase in release of ACh induced by DOI in the prefrontal cortex, but not in the hippocampus, appears to be due to 5-HT2 receptor mechanisms localized within this brain region. Furthermore, it appears that the prefrontal cortex is more sensitive than the dorsal hippocampus to the stimulatory effect of 5-HT2 agonists on ACh release.

Acetylcholine↗