Kinetic approach to determine the generation rate of available surface area during the dissolution process.
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The agonistic action of fenamates on the alpha 1-adrenoceptor-activated cationic current (Icat) in rabbit portal vein smooth muscle was investigated with the whole-cell patch clamp technique. At -50 mV, the fenamates (100-500 microM) increased Icat dose-dependently, up to several fold. This increase was not accompanied by changes in the reversal potential and strongly inhibited by 500 microM Cd2+ or 10 mM procaine. The enhancing effect of fenamates was also observed on the cationic current activated by intracellularly applied GTP gamma S. These results suggest that fenamates may be useful as a new class of activator for receptor-operated cation channels in smooth muscle.
The addition of luteinizing hormone releasing hormone releasing hormone (LH-RH) to cultures of monolayers of rat anterior pituitary cells was shown to increase both the concentrations of prostaglandins E1 and E2 (PGE) in the cells and the release of LH over similar ranges of concentrations of LH-RH (10(-6) to 10(-10) mol/l). The peak concentration of PGE was observed after 2.5 h. The stimulation of the level of PGE in the cells by LH-RH was completely inhibited by two inhibitors of prostaglandin synthetase, which only partially inhibited the stimulation of LH release. Therefore the increased concentration of PGE was not obligatory for the effect of LH-RH on LH release. It was also shown that monobutyryl cyclic AMP stimulated the intracellular concentration of PGE and it is suggested that the stimulation of PGE levels may be mediated by increased levels of cyclic AMP in the cells after the addition of LH-RH.
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A number of drugs are available that act fairly specifically as "mild" analgesics, although this description by no means implies that their clinical effectiveness is limited to the relief of slight pain and trivial disability. They are effective by mouth and their action is mediated peripherally. Among the possible mechanisms of action, the inhibition of prostaglandin synthesis is currently regarded as most likely to be relevant. Some centrally acting drugs of the narcotic analgesic type, such as codeine and dextropropoxyphene are effective orally; they are usable in the same way as other mild analgesics and may be preferable for some types of pain. Many problems arise in the assessment and comparison of mild analgesics, both experimentally and clinically. Subjective assessments may be made on a pain scale by the patient himself, or by a trained observer. Individual variations are all-important, and the limitations of controlled trials need to be remembered. Alternative drugs and mixtures have little advantage over aspirin, but specific drug tolerance, in the long term, varies from patient to patient. Gastric irritation is most likely to occur with aspirin in the presence of chronic dyspepsia or acute precipitating causes such as alchoholic gastritis. Allergy also occurs in some susceptible individuals. The risk of renal damage with phenacetin is increasingly appreciated, and the possibility of hepatic damage from paracetamol is now recognised. Other side-effects and interactions are summarized in the review, and some notes are given on therapeutic and non-therapeutic use.
A survey of earlier published studies on treatment of dysmenorrhea with prostaglandin synthetase inhibitors is given and personal clinical experiences are presented. The time when treatment should start in relation to the onset of bleeding is also discussed. A survey of studies published in English and Scandinavian literature yielded 532 patients. Pain relief was experienced in 64 to 100 per cent of the patients in these studies. The incidence of side-effects has generally been low but in a few studies a high incidence was reported. In the current study 34 patients with prinary dysmenorrhea completed the douule-blind, placebo controlled study on naproxen. The patients were treated for two cycles, 16 with naproxen and 18 with placebo. The mean relief score indicated a "slight to good" pain relief in the naproxen group and "no alleviation" in the placebo group. The difference is statistically significant (p = 0.003). Supplementary medication was much more used in the placebo group compared to the naproxen group (p = 0.01). In the placebo group no change whatsoever was demonstrated in alleviation of interference with every-day life, whereas there was a statistically significant improvement in the naproxen group. No major side-effect was registered. Thus none of the subjects withdrew from the study.
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