Narcotic Antagonists

Archer, Sydney; Harris, Louis S.

doi:10.1007/978-3-0348-7056-6_4

Cited by 8 publications

(12 citation statements)

References 120 publications

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“…Consistent with previous findings (Archer & Harris, 1965 ;Pearl et al, 1968), (-cis-I (C-S ethyl homologue of 1-pentazocine) acted like an opiate antagonist, while its trans isomer acted like an opiate. Although the cis form rather than the trans form is more closely related sterically to the cis-fused B/C ring system of morphine (Fullerton, May & Becker, 1962), the unnatural trans-fused ring system may often afford better access to or fit on the receptor.…”

Section: Discussionsupporting

confidence: 92%

“…Structure-activity relations for optical and geometric isomers of benzomorphan derivatives were studied because changes in the isomerism of these derivatives evidently not only affects the degree of activity exhibited but whether opiate-like or antagonist effects are exhilbited (Archer, Harris, Alibertson, Tullar & Pierson, 1964;Archer & Harris, 1965;Tullar, Harris, Perry, Pierson, Soria, Wetterau & Albertson, 1967;Pearl, Aceto & Harris, 1968).…”

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confidence: 99%

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Effects of opiates and opiate antagonists on the Straub tail reaction in mice

Aceto

McKean

Pearl

1969

British J Pharmacology

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. Subcutaneous injections of opiates produced the Straub tail reaction in mice. The potencies of the opiates in mice were consistent with previous estimates of the analgesic potencies in animals and in man. . The potencies of sixteen antagonists in counteracting the reaction were consistent with those previously obtained with the rat tail‐flick test. . The (–) isomers of four benzomorphan derivatives were much more potent in counteracting the reaction than their (+) isomers and about twice as potent as their racemates. The activity of the isomers seemed to follow Pfeiffer's rule: the lower the effective dose of a drug, the greater the difference in the pharmacological effects of the optical isomers. One of the trans isomers acted like an opiate, while its cis isomer acted like an antagonist. . Naloxone and nalorphine fulfilled conventional criteria for competitive antagonism, whereas atropine and the (–) and the (+) isomers of pentazocine and of cyclazocine did not do so. . The Straub tail test seems to be useful for studying structure‐activity relations among opiates and opiate antagonists.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Effects of opiates and opiate antagonists on the Straub tail reaction in mice

Aceto

McKean

Pearl

1969

British J Pharmacology

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“…Der Rattenschw anzreaktionstest von D'Amour-Smith [1] und der Mäusetest von Eddy und Leimbach [7] gaben über die so er zeugte W irkung eher Aufschluss als über die klinisch analgetische W irksamkeit [4]. Bei R attentests jedoch haben Evans und Bergner [9,10] nachgewiesen, dass die analgetische W irkung von Pentazocin etwa y4 bis 1/5 der von Morphin beträgt.…”

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Erfahrungen mit Pentazocin (Win 20.228) in der Geburtshilfe

Massinger

Lazaridis

1968

Gynecol Obstet Invest

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“…about four to six times as potent as nalorphine in antagonizing the effects of morphine. meperidine, and phenazocine [23]. It is an agonist-antagonist and.…”

Section: Topographical Analysismentioning

confidence: 99%

“…Many of the narcotic agonist-antagonists are so strongly psychotomimetic that they are contraindicated for clinical usage [23]. In a very recent article by Pauling and coworkers [24] were set forth "approximate but not exact relationships between what may be pharmacodynamic groups essential for hallucinogenic activity.''…”

Section: Topographical Analysismentioning

confidence: 99%

Quantum chemical, other theoretical and physicochemical studies on narcotics and narcotic antagonists to understand their mechanism of action

Kaufman

Kerman

Koski

2009

Int. J. Quantum Chem.

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The topological and topographical requisites for effective narcotic and narcotic antagonist action are outlined. Quantum chemical calculations by several methods have been carried out for these drugs. c N t m I I and PCILO results are compared for morphine and nalorphine. both for the free bases and the protonated forms. CNUOi2 results are presented for some additional narcotics and narcotic antagonists: naloxone. cyclazocine. and methadone. The CNDO/2 calculated electron densities on the nitrogens are very close in the free bases of the N-methyl and the N-ally1 cogeners and they are also very close in the protonated forms of thcse compounds. contrary to the assumption usually held by chemists that the electron density on the nitrogen is lower in the ally1 compound which is what makes it a weaker base. Also. as we tirst showed many years ago for pyridine aldoximes the positive charge in the N-protonated species is not localized on the nitrogen but spread over many of the neighboring atoms. Both of the above results on the charge distributions on the nitrogens were experimentally given credence by the ESCA results of Carlson and Saethre. Narcotic action had previously been shown to be governed both by the pharmacological interaction of the drug and by its lipophilicity which is necessary to pass through the blood brain barrier. Use of a special titrimetric technique enabled us to measure not only the pK,'s but also the partition coefficients as a smoothly varying function of pH.The pertinent background data on the effects of narcotics and narcotic antagonists on biogenic amine turnover. synthesis. release. etc.. are reviewed in a brief comprehensive manner. We performed an intensive systems analysis of these data and were able to postulate the mechanism by which a narcotic causes addiction and. thus. to suggest a new method of treating addiction which does not use either maintenance on synthetic narcotics or on narcotic antagonists. Our analysis also indicates a mechanism of action of narcotic antagonists (which we do not feel is merely competitive antagonism). A comparison of the psychotomimetic symptoms caused by narcotic antagonists with those caused by the LSD and mescaline groups on the one hand and by the anticholinergics on the other hand indicate pertinent similarities.

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Narcotic Antagonists

Cited by 8 publications

References 120 publications

Effects of opiates and opiate antagonists on the Straub tail reaction in mice

Effects of opiates and opiate antagonists on the Straub tail reaction in mice

Erfahrungen mit Pentazocin (Win 20.228) in der Geburtshilfe

Quantum chemical, other theoretical and physicochemical studies on narcotics and narcotic antagonists to understand their mechanism of action

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