The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

State of the art in hair analysis for detection of drug and alcohol abuse.

Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that Salvinorin A potently and selectively inhibited 3H-bremazocine binding to cloned κ opioid receptors. Salvinorin A had no significant activity against a battery of 50 receptors, transporters, and ion channels and showed a distinctive profile compared with the prototypic hallucinogen lysergic acid diethylamide. Functional studies demonstrated that Salvinorin A is a potent κ opioid agonist at cloned κ opioid receptors expressed in human embryonic kidney-293 cells and at native κ opioid receptors expressed in guinea pig brain. Importantly, Salvinorin A had no actions at the 5-HT2A serotonin receptor, the principal molecular target responsible for the actions of classical hallucinogens. Salvinorin A thus represents, to our knowledge, the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist. Because Salvinorin A is a psychotomimetic selective for κ opioid receptors, κ opioid-selective antagonists may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that κ opioid receptors play a prominent role in the modulation of human perception.

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Salvinorin A: A potent naturally occurring nonnitrogenous κ opioid selective agonist

A number of aposematic butterfly and diurnal moth species sequester unpalatable or toxic substances from their host plants rather than manufacturing their own defensive substances. Despite a great diversity in their life histories, there are some general features in the selective utilization of plant secondary metabolites to achieve effective protection from predators. This review illustrates the biochemical, physiological, and ecological characteristics of phytochemical-based defense systems that can shed light on the evolution of the widely developed sequestering lifestyles among the Lepidoptera.

Sequestration of defensive substances from plants by Lepidoptera.

Background: The purposes of this study were to investigate the pharmacokinetics of methylphenidate hydrochloride (Ritalin) in the human brain, to compare them with those of cocaine, and to evaluate whether cocaine and methylphenidate compete for the same binding sites. Methods: We used positron emission tomography to measure the temporal and spatial distribution of carbon 11 (11C)-labeled methylphenidate. These results were compared with those obtained previously for [11C]cocaine. Eight healthy male subjects, 20 to 51 years of age, were scanned with [11C]methylphenidate. Three were tested twice to assess test-retest variability, four were tested at baseline and after administration of methylphenidate, and one was tested with [11C]methylphenidate and [11C]cocaine. Two baboons were scanned to evaluate whether there was competition between cocaine and methylphenidate for the same binding sites in the brain. Results: The uptake of [ 11 C] methylphenidate in the brain was high (mean±SD, 7.5%±1.5%), and the maximal concentration occurred in striatum. Pretreatment with methylphenidate decreased binding only in striatum (40%). Although the regional distribution of [ 11 C]methylphenidate was identical to that of [ 11 C] cocaine and they competed with each other for the same binding sites, these two drugs differed markedly in their pharmacokinetics. Clearance of [ 11 C]methlphenidate from striatum (90 minutes) was significantly slower than that of [ 11 C]cocaine (20 minutes). For both drugs, their fast uptake in striatum paralleled the experience of the "high." For methylphenidate, the high decreased very rapidly despite significant binding of the drug in the brain. In contrast, for cocaine, the decline in the high paralleled its fast rate of clearance from the brain. Conclusion: We speculate that because the experience of the high is associated with the fast uptake of cocaine and methylphenidate in the brain, the slow clearance of methylphenidate from the brain may serve as a limiting factor in promoting its frequent self-administration.

Is Methylphenidate Like Cocaine?: Studies on Their Pharmacokinetics and Distribution in the Human Brain

The Sharanahua and Culina, small Indian tribes located in the southwestern Amazon basin, use a hallucinogenic drink for medicinal and social purposes. This decoction, called “Ayahuasca” in Peru, is prepared from Banisteriopsis Caapi stems and Psychotria sp. leaves. These plants have been botanically identified on the basis of voucher herbarium specimens and investigated for alkaloid content by means of a gas chromatography-mass spectrometry technique. A list of other occasional plant admixtures is given. Harmine, Harmaline, Tetrahydroharmine, Harmol and 6-Methoxytryptamine have been found in Banisteriopsis Caapi. Dimethyltryptamine, Monomethyltryptamine and 2-methyl-1,2,3,4-tetrahydro-β-carboline have been found in Psychotria viridis and Psychotria carthaginensis. Harmine, Harmaline, Tetrahydroharmine and Dimethyltryptamine have been found in the drink. Quantitative calculations show the amount of each alkaloid administered in the Ayahuasca drink.

“Ayahuasca,” the South American hallucinogenic drink: An ethnobotanical and chemical investigation

We report the findings of the analysis of 75 different nutritional supplements bought through the internet. Seven products (all from the class of prohormones) contained other hormone substances than indicated on the labels, and two further products contained ephedrine and caffeine without a clear indication on the labels.

Nutritional Supplements as a Source for Positive Doping Cases

Quantitative analysis of indolyl-3-acetic acid (IAA) in different parts of maize root tips (Zea mays L. cv. Kelvedon 33) were performed by selective ion current monitoring detection (or mass fragmentography). It was found that the cap contained 356.6±16.2 μg of IAA kg(-1) fresh weight; the apex had only half this concentration of IAA. Calculations indicated that the 10-mm apical segments of the root contained 109.6 μg kg(-1) fresh weight. The possibility that the growth regulator formed in the cap and inhibiting the elongation of the extension zone of the root is IAA is discussed.

L. Rivier

Papers

“Ayahuasca,” the South American hallucinogenic drink: An ethnobotanical and chemical investigation

Nutritional Supplements as a Source for Positive Doping Cases

Indolyl-3-acetic acid in cap and apex of maize roots: Identification and quantification by mass fragmentography.

Drugs and alcohol among suspected impaired drivers in Canton de Vaud (Switzerland).

Salvia divinorum: an hallucinogenic mint which might become a new recreational drug in Switzerland.