Narcotic activities

Meyer H. On the theory of alcohol narcosis. I. Which property of anesthetics gives them their narcotic activity Arch Exper Pathol Pharmakol 1899 42 109-18. 

Dittman EC, Etschenberg E. 1973. Endoanesthetic and narcotic activity of halogenated methane derivatives. Eur J Pharmacol 24 389-398. 

The generalized connectivity indices hxR and Xr have found numerous applications to structure-activity correlations, reviewed in the book of Kier and Hall8). Anaestetic activity was studied most detailed 6 13), along with nonspecific narcotic activity 8,14), enzyme inhibition 8,15,17) etc. 

Si,Si-Dimethyl-Sila-Substituted Derivatives of Spirobarbiturates with Narcotic Activity... 

Even the simplest 1-organylsilatranes potentiate the narcotic activity of hexa-barbital33. They possess an analgetic and sedative effect. 1-Methylsilatrane is most active in this respect. 

Membranes Inhalation anaesthetics (diethylether, chloroform, and their more modem replacements). The mode of action of these was enshrouded in mystery for a long time, but accumulating evidence now supports direct interaction with several ion channels. Nevertheless, there is a remarkably close correlation between the ability of these agents to partition into lipid membranes, as measured by their oil-water partition coefficients, and their narcotic activity so, in a sense, cell membranes may be considered the targets of these agents. 

In classical structure-activity studies, most of the attempts concentrated on correlating the activity with one of the molecular properties— e.g., the carcinogenic activity of polynuclear aromatic compounds with their electronic structure (18, 19), the narcotic activity with lipophilicity 20, 21), the insecticidal activity of cyclodienes with their three-dimensional molecular silhouette 22), etc. Sometimes the activity correlated well with only one of the molecuar parameters. In our approach these are special cases where other physicochemical properties do not play critical roles in determining the variation in the activity within a set of congeners so that the coefficients defining these other properties are zero. 

Basak and Magnuson correlated the nonspecific narcotic activity (LC50) of alcohols using Us ... 

Structurally non-specific action is usually due to the accumulation of a drug in an important part of a cell which possesses dominant lipid characteristics. Substances like alkanes, alkenes, alkynes, ketones, amides, ehlorinated hydro-carbons, ethers and alcohols display narcotic activity which is directly proportional to the partition coefficient of each individual substances. 

In 1899 Overton (13) and Meyer (1 ) correlated narcotic activity with lipid solubility (chloroform-water partition coefficients) of a wide variety of non-ionized compounds. They found that narcotic activity increased with increasing lipophilicity until lipid solubility became so high that the substance was virtually water insoluble. They also found that these compounds penetrated tissue cells as though the membranes were lipid in nature. This is the first reported correlation between partition coefficients and biological activity. A second major development in QSAR occurred in 1939 when Ferguson (15) was able to calculate toxic concentrations of a series of compounds from solubility and vapor pressure data. 

Use activity H. are used in pharmacological research, they may have significance in the development of alcoholism, and are considered to be metabolites of tryptamine. Plasma levels of barman in heroin-depen-dent and methadone-substituted patients are elevated by ca. 200%. H. have hallucinogenic and narcotic activities. Extracts of the above-mentioned plants are thus used by traditional healers in central Asia. South American Indians and mestizos use the macerated bark of B. caapi as a hallucinogenic drink (ayahuasca= liana of the soul, also Yaje, Caapi), the effects begin with nervousness, sweating, nausea, and then intoxication states (visions in brilliant colors), dream-like... 

Table 109 a. Experimental condition for TLC of analgesics with narcotic activity... 

MUT, mutagenic and neoplastic activity NEU, neurotoxic and narcotic activity OXD, oxidizing agent POX, forms explosive peroxides SHK, explosive hazard from shock SKN, penetrates intact skin TOX, highly toxic WRX, reacts with water... 

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