Journal of Pharmacology and Experimental Therapeutics 

About: Journal of Pharmacology and Experimental Therapeutics is an academic journal published by American Society for Pharmacology and Experimental Therapeutics. The journal publishes majorly in the area(s): Receptor & Agonist. It has an ISSN identifier of 0022-3565. Over the lifetime, 32242 publications have been published receiving 1502940 citations. The journal is also known as: The Journal of pharmacology and experimental therapeutics.

A simplified method of evaluating dose-effect experiments

Abstract: 1. A rapid graphic method for approximating the Median Effective Dose and the Slope of dose-per cent effect curves is presented. Confidence limits of both of these parameters for 19/20 probability are given by the method. In addition, confidence limits for any other probability or for a dose other than the Median Effective Dose are readily estimated. 2. The data are used throughout the method in their original form without transformation to logarithms and probits. 3. An effective means for plotting and using 0 and 100 per cent effects is provided. 4. The calculations have been simplified by means of nomographs to the extent that a slide rule is a convenience but not a necessity. 5. A simple means is provided for detecting a poorly fitted line or significantly heterogeneous data, In the former case, the line may be refitted; in the latter, the confidence limits are corrected for the degree of heterogeneity. 6. The method provides means for the rapid test of parallelism of two curves and easy computation of relative potency with its confidence limits. 7. Although the method is rapid (10-15 minutes), its accuracy is commensurate with the nature of dose-per cent effect data.

A method for determining loss of pain sensation

Abstract: 1. A simple, rapid method for determining the pain threshold in the rat is described. 2. The individual variation, under a variety of conditions, was found to be surprisingly small. 3. The method was applied to the determination of analgesic properties of several substances, including cobra venom. No analgesic property in the latter could be demonstrated. 4. A comparative assay of five opiates gave results in good agreement with clinical experience.

The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog.

Abstract: Three different syndromes produced by congeners of morphine have been identified in the nondependent chronic spinal dog. These syndromes have been attributed to interaction of agonists with three distinguishable receptors (mu, kappa and sigma). Morphine is the prototype agonist for the mu receptor, ketocyclazocine for the kappa receptor and SKF-10,047 for the sigma receptor. The morphine syndrome (mu) in the dog is characterized by miosis, bradycardia, hypothermia, a general depression of the nociceptive responses and indifference to environmental stimuli. Ketocyclazocine (kappa) constricts pupils, depresses the flexor reflex and produces sedation but does not markedly alter pulse rate or the skin twitch reflex. SKF-10,047 (sigma), in contrast to morphine and ketocyclazocine, causes mydriasis, tachypnea, tachycardia and mania. The effects of these three drugs can be antagonized by the pure antagonist naltrexone, indicating that they are agonists. Further, chronic administration of morphine, ketocyclazocine and SKF-10,047 induces tolerance to their agonistic effects. Morphine suppresses abstinence in morphine-dependent dogs while ketocyclazocine does not. Ketocyclazocine at best precipitated only a liminal abstinence syndrome in the morphine-dependent dog, indicating that it had little affinity for the morphine receptor. Ketocyclazocine thus appears to be a selective agonist at the kappa receptor. Further, it has been shown that buprenorphine is a partial agonist of the mu type which both suppressed and precipitated abstinence in the morphine-dependent dog while morphine and propoxyphene are stronger agonists. Apomorphine and SKF-10,047 produce similar pharmacologic effects suggesting that sigma activity may involve a dopaminergic mechanism.

Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians.

Abstract: Interindividual variations in the level and activity of cytochrome P-450 enzymes were investigated in the liver microsomes of 30 Japanese and 30 Caucasian patients. The P-450 enzymes used in this study included P-450 1A2, 2A6, 2B6, 2C, 2D6, 2E1 and 3A, and the monooxygenase activities determined were 13 typical P-450 substrates and 9 procarcinogens. Although the total P-450 content was higher in Caucasian (mean, 0.43 nmol/mg of protein) than in Japanese populations (mean, 0.26 nmol/mg of protein), the relative levels (percent of total P-450) of individual forms of P-450 determined immunochemically were not very different except that P-450 2A6 and 2B6 levels were higher in the Caucasians. About 70% of liver P-450 could be accounted for by P-450 1A2, 2A6, 2B6, 2C, 2D6, 2E1 and 3A proteins, and P-450 3A (about 30% of total P-450) and 2C (about 20%) enzymes were found to be the major forms. Considerable levels of P-450 1A2 (about 13%) and 2E1 (about 7%) could be determined, whereas the P-450 2A6 (about 4%), 2D6 (about 2%) and 2B6 (< 1%) were the minor P-450 forms. Differences in some of the P-450 1A2-, 2A6-, 2D6-, 2E1- and 3A4-dependent activities were observed in Japanese and Caucasian populations. No clear sex-related differences in individual P-450 contents and drug- and carcinogen-metabolizing activities were detected in 60 human samples, except that P-450 1A2-dependent activities were found to be higher in mean than in women in the Caucasian population only. A single neonate sample tended to be lower in P-450 1A2-, 2A6- and 2E1-dependent activities. In contrast to rat counterparts, we could not detect apparent developmental changes in P-450 content and activity in humans between 12 and 73 years old. Thus, the results presented in this study provide useful information for the study of drug biotransformation in humans and for the basis of drug toxicities, carcinogenesis and teratogenesis.