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529 On the pharmacology of reactivity experiments with ginseng
Abstracts br a factor in limiting renal concentrating ability in addition to other known factors.153 s, ‘9 s, s,
1. I\IARTIN~IC, .A. (19361,
Butterworths,
London.
8. KLEEV.~, Cl.R., PURSEL, S. and HENDRIKX. (19571, 3. Clin. Zniest., 36, 635. 9. EDELMANN, C. hf.,JR.,BARNETT,H. L. and rao~~~ou, 1’. (1960), .3. Clin. Znmt., 39, 1062. 527 Accumulation
of “9 labelled Guinea Pig Kidney Slices. H. SCIINIEW~ND (Gchrmany).
Probenecid in LV. BRAUN and
of Papers
159
pregnancy, the author investigated the effect of a placental extract in patients with this disease. This is a controlled study of the effects of a Eighty-foul placental extract in osteoarthritis. patients with osteoarthritis were studied in a doublr blindfold manner: one half received a placebo and The the other half received the placental extract. placental extract was a crystalline preparation which was injected subcutaneously in doses of 150 mg once or twice weekly. The cases WCI‘IC followed for one year. Xroderate to excellent subjective and objective improvement was observed in 91 per cent of thr placental treated patients as opposed to 15 per cent of the control group. There were no toxic mani!&ations, no evident? of sensitivity or diminishing response to therapy in Their functional the placental-treated group. capacity as well as their sense of well being was improved. The incidence of destructive bonr lesions by I’oentgen examination was reduced and the improvement was still evident to a significant extent at the end of the yrar. From the results, the author b&eves that osteoarthritis is a deficiency disease caused by an inhorn error of metabolism and that this deficiency may be corrected by replacemrnt therapy with the placental extract which probably controls the release of essential hormones. Excellent results can be obtained in many patients by the relief of joint pain and swelling, often \vith long-term beneficial effects.
The excretion of acti\,ely transportrd organic acids across the renal tubular cells is inhibited by probrnrcid. The mode of action of this effect is not undrrstood as yet. Beyer hay shown that the parent compound p-carboxybenzenesulphonamidc itself is secreted. To study this problem further, experiments have 529 On the Pharmacology of Reactivity (Experibeen perfcommcd with the aid of 3% labelled pro\-. PETKOV (Bulgaria). ments with Ginseng). benerid. It was found that probenecid was highly concentrated in rat kidneys following a single Pharmacological substances should be considered injection. Relative concentrations in kidney, liver. and studied not only as factors which can change heart and skeletal muscle were 100, 27, 12 and 2 the functions of the organism in one direction or respectively. Furthermore, accumulation of proanother but also as factors which, without even bcnecitl in kidney slices ha* been investigated by the provoking directly manifested effects, can change method of Cross and Taggart and Beyer et al. the reactivity of structures of the organism in such a Probenccid is readily taken up and highly concenmanner that the subsequent (or simultaneous\ Plotting the trated by guinea-pig kidney slices. influence of most varied factors (including also srlbstran.concentration against accumulated amount pharmacological ones) would result in a reaction yields a caturation typr curve, the hlicharlis conOn the othcl different from that usually expected. stant of which is calculated to be 4.10-j &I. hand, one would think that by means of such pharFrom these results we may conclude that promacological substances we should also be able to bcnecid is also actively transported by the renal influence, in a dirrction we desire, thepathologicall) tubule,. Its affinity to the carrier system however changed reactivity in morbid conditions. is about 13 times as great as that of PXH. ProIn experiments with ginseng it has been rstabbcnecitl therefore stems very likely to act as a lishrd that extracts from the roots of this plant competitivr inhibitor like bromcresolgreen and facilitate the formation of conditionrd reflexes 01 bromphcnolbluc with high affinities and low turnsignal stimuli and make possiblr the manifestation over. though the Lincvcawer~Burk plot shows tllc of the rffect of subthrcshold doses of phenaminc charact<&tics of a non-competitive inhibition. At thr stimulating the conditioned retlex activity. same time, EEG investigations show that ginseng facilitates the occurrence of primary evoked poten528 Osteoarthritis Treated with a Placental tials. In experiments on a straight abdominal Extract. A Double Blind Study. I.. I\‘. muscle of a frog, in a combined application of ginGRANIRER (U.S.h.). seng and acetylcholine, a potrntiation of the effects is ohservrd. In threshold concentrations, ginseng Imprrsscd by the rarity of osteoarthritis during
160
ilbstracts
and acetylcholine mutually potentiate their stimulating action on the intestinal motility. ‘Ihe results obtained from further experiments with pendiomide, glutaminic acid, escrine, tuborurarine, CdCI,, KCl, atropine, BaCl, and histamine suggest that the influence of ginseng on the reactivity of the nervous and muscular elements is primarily due to its influence on the intracellular potassium storage. The effects of applying ginseng may only partially be explained as the result of its direct stimulating action. The operation of ginseng should be assessed much more as a consequence of its influence on the readiness of the nervous and muscular and perhaps of other physiological systems to react to some or An attempt is being made to subother stimuli. stantiate a new pharmacology of reactivity.
530 Hormonal Effects of Different SHARAP and I. _Ava.
Plants.
of
Papen
531 Mode of Action of Nigellone. 51. EL-DAKHAKHNY (U.A.R.).
Nigcsllonc is the active principle of the seed oil 01 .\&lla scltiz.a L, which has recently been isolated in this department in a pure crystalline form and was shown to pcrsscss a molecular formula of C,,H,,O,. The most prominent pharmacological property 01 Nigellonc was its power to protect guinea pigs against histamine-induced bronchospasm, a property- present in the mother oil to a wry small degree. It also proved to be a valuable therapeutic aid in the control of bronchial asthma in children and adults. Administered as oral drops it was usctl in the trcatmcnt of over 200 cases with favourable improvement in about 70 per cent of cases. Nigcllone had no toxic effects even when given in large doses to men or in animal experiments. The possible mechanism of this action was investigatcd. Stimulation of the adrrnergic mechanism coulcl not be demonstrated especially if other pharmacological actions of the drug are considered, e.g. no vasoconstrictor effect on pet&cd blood vessels, nor any hypertensive effect on experimental animals There was also no evidence that Nigellone or man. had a blocking action on the peripheral cholinrrgic mechanism as it did not antagonize the eflccts 01 acctylcholinc on the bronchi, intestines. etc. The available evidence points to the fact that the drug is transformed to an active form in the blood which inhibits the dynamic activity of the plain muscle fusiform cell membrane.
i\.
\Vhm the oestrogenic, androgenic, progcstational and gonadotrophic effects were examined, it was found that different plant preparations possess some The sweet orange of these hormonal properties. juice and ascorbic acid produced endometrial progestational proliferati\re reactive. In this respect, it possesses a progcsteronc-like activity and may be used alone or in combination with progesterone in all conditions associated with low level of progcsteronc as in habitual and threatened abortions. &er mienturn,has been experimentally proved to produce androgenic activity as it increased the weights of the prostates and seminal vesicles of castrated male rats, and progesterone-like action as it produced progcstational proliferation in the endometrium of ovariectomized rabbits. Catha edule leaves, when fed to animals, also produced progestational prliferation in the endometrium of rabbits resembling that of progesterone. On feeding Egyptian clover to immature rabbits it increased the uterine weights to a considerable extent; this indicates that clover possesses oestrogenic activity. The oxytocic effect of different plant preparations has been investigated in hq on the uterus of animals at various stages of the sex cycle and after Quinine produced strong hormonal treatments. stimulation of the uterine muscle of pregnant rats and ovariectomized animals treated with progesterone. The effect was less marked on the uterus of oestrous rats and of ovcriectomized animals treated with ocstradiol. Quinine also increased the uterine response of the pregnant uterus to the posterior pituitary extract. Cotton root bark extract increased the uterine motility ofthe pregnant uterus and that of ovariectomtzed ammals treated with progesterone, whereas, it inhibited that of oestrous and ovariectomized rats treated with oestradiol. On the other hand, Lupinus termis seed extract produced consistent motor effects on the uterus of all animals whatever the state of the uterus.
hf. ~WWFOUZ and
532 Antitussive Action of Oxolamine (3-Phenyl-5$-Diethylaminoethyl-1:2:4-Oxadiazole). B. SIL~~ESTRI~~ (Italy). (J-phcnyl-5-B-diethylaminoethyla new compound synthetized and studied in the .Angelini Research L,aboratorirs, presents the following properties: (a) an antitussive action (b) an analgesic-anti-inflammatory action of the aspirin-type (c) a spasmolytic action of the papaverine-type Id) a mild antipyretic and local anaesthetic action. The antitussivr action of oxolamine is particularly evident against experimental cough induced by irritating vapours, which produce inflammation and spasm of the bronchial tree. Oxolamine is less active against centrally evoked cough. The possibility is therefore discussed that the antitussive action of oxolamine is taking place through a synergrsm between the mild depressive action on the coughing centre and the anti-inflammatory and spasmolytic properties. Oxolamine
1 ::! :+oxadiazole),
533
The Behaviour of Hypertensive Drugs on the Suprarenal Gland and Kidney Perfusion in the Cat. P. D. GARCIA DE JALON and L. .A. L. SAxros (Spain). The
pharmacological
controls
of
5HT
were
1. I\IARTIN~IC, .A. (19361,
Butterworths,
London.
8. KLEEV.~, Cl.R., PURSEL, S. and HENDRIKX. (19571, 3. Clin. Zniest., 36, 635. 9. EDELMANN, C. hf.,JR.,BARNETT,H. L. and rao~~~ou, 1’. (1960), .3. Clin. Znmt., 39, 1062. 527 Accumulation
of “9 labelled Guinea Pig Kidney Slices. H. SCIINIEW~ND (Gchrmany).
Probenecid in LV. BRAUN and
of Papers
159
pregnancy, the author investigated the effect of a placental extract in patients with this disease. This is a controlled study of the effects of a Eighty-foul placental extract in osteoarthritis. patients with osteoarthritis were studied in a doublr blindfold manner: one half received a placebo and The the other half received the placental extract. placental extract was a crystalline preparation which was injected subcutaneously in doses of 150 mg once or twice weekly. The cases WCI‘IC followed for one year. Xroderate to excellent subjective and objective improvement was observed in 91 per cent of thr placental treated patients as opposed to 15 per cent of the control group. There were no toxic mani!&ations, no evident? of sensitivity or diminishing response to therapy in Their functional the placental-treated group. capacity as well as their sense of well being was improved. The incidence of destructive bonr lesions by I’oentgen examination was reduced and the improvement was still evident to a significant extent at the end of the yrar. From the results, the author b&eves that osteoarthritis is a deficiency disease caused by an inhorn error of metabolism and that this deficiency may be corrected by replacemrnt therapy with the placental extract which probably controls the release of essential hormones. Excellent results can be obtained in many patients by the relief of joint pain and swelling, often \vith long-term beneficial effects.
The excretion of acti\,ely transportrd organic acids across the renal tubular cells is inhibited by probrnrcid. The mode of action of this effect is not undrrstood as yet. Beyer hay shown that the parent compound p-carboxybenzenesulphonamidc itself is secreted. To study this problem further, experiments have 529 On the Pharmacology of Reactivity (Experibeen perfcommcd with the aid of 3% labelled pro\-. PETKOV (Bulgaria). ments with Ginseng). benerid. It was found that probenecid was highly concentrated in rat kidneys following a single Pharmacological substances should be considered injection. Relative concentrations in kidney, liver. and studied not only as factors which can change heart and skeletal muscle were 100, 27, 12 and 2 the functions of the organism in one direction or respectively. Furthermore, accumulation of proanother but also as factors which, without even bcnecitl in kidney slices ha* been investigated by the provoking directly manifested effects, can change method of Cross and Taggart and Beyer et al. the reactivity of structures of the organism in such a Probenccid is readily taken up and highly concenmanner that the subsequent (or simultaneous\ Plotting the trated by guinea-pig kidney slices. influence of most varied factors (including also srlbstran.concentration against accumulated amount pharmacological ones) would result in a reaction yields a caturation typr curve, the hlicharlis conOn the othcl different from that usually expected. stant of which is calculated to be 4.10-j &I. hand, one would think that by means of such pharFrom these results we may conclude that promacological substances we should also be able to bcnecid is also actively transported by the renal influence, in a dirrction we desire, thepathologicall) tubule,. Its affinity to the carrier system however changed reactivity in morbid conditions. is about 13 times as great as that of PXH. ProIn experiments with ginseng it has been rstabbcnecitl therefore stems very likely to act as a lishrd that extracts from the roots of this plant competitivr inhibitor like bromcresolgreen and facilitate the formation of conditionrd reflexes 01 bromphcnolbluc with high affinities and low turnsignal stimuli and make possiblr the manifestation over. though the Lincvcawer~Burk plot shows tllc of the rffect of subthrcshold doses of phenaminc charact<&tics of a non-competitive inhibition. At thr stimulating the conditioned retlex activity. same time, EEG investigations show that ginseng facilitates the occurrence of primary evoked poten528 Osteoarthritis Treated with a Placental tials. In experiments on a straight abdominal Extract. A Double Blind Study. I.. I\‘. muscle of a frog, in a combined application of ginGRANIRER (U.S.h.). seng and acetylcholine, a potrntiation of the effects is ohservrd. In threshold concentrations, ginseng Imprrsscd by the rarity of osteoarthritis during
160
ilbstracts
and acetylcholine mutually potentiate their stimulating action on the intestinal motility. ‘Ihe results obtained from further experiments with pendiomide, glutaminic acid, escrine, tuborurarine, CdCI,, KCl, atropine, BaCl, and histamine suggest that the influence of ginseng on the reactivity of the nervous and muscular elements is primarily due to its influence on the intracellular potassium storage. The effects of applying ginseng may only partially be explained as the result of its direct stimulating action. The operation of ginseng should be assessed much more as a consequence of its influence on the readiness of the nervous and muscular and perhaps of other physiological systems to react to some or An attempt is being made to subother stimuli. stantiate a new pharmacology of reactivity.
530 Hormonal Effects of Different SHARAP and I. _Ava.
Plants.
of
Papen
531 Mode of Action of Nigellone. 51. EL-DAKHAKHNY (U.A.R.).
Nigcsllonc is the active principle of the seed oil 01 .\&lla scltiz.a L, which has recently been isolated in this department in a pure crystalline form and was shown to pcrsscss a molecular formula of C,,H,,O,. The most prominent pharmacological property 01 Nigellonc was its power to protect guinea pigs against histamine-induced bronchospasm, a property- present in the mother oil to a wry small degree. It also proved to be a valuable therapeutic aid in the control of bronchial asthma in children and adults. Administered as oral drops it was usctl in the trcatmcnt of over 200 cases with favourable improvement in about 70 per cent of cases. Nigcllone had no toxic effects even when given in large doses to men or in animal experiments. The possible mechanism of this action was investigatcd. Stimulation of the adrrnergic mechanism coulcl not be demonstrated especially if other pharmacological actions of the drug are considered, e.g. no vasoconstrictor effect on pet&cd blood vessels, nor any hypertensive effect on experimental animals There was also no evidence that Nigellone or man. had a blocking action on the peripheral cholinrrgic mechanism as it did not antagonize the eflccts 01 acctylcholinc on the bronchi, intestines. etc. The available evidence points to the fact that the drug is transformed to an active form in the blood which inhibits the dynamic activity of the plain muscle fusiform cell membrane.
i\.
\Vhm the oestrogenic, androgenic, progcstational and gonadotrophic effects were examined, it was found that different plant preparations possess some The sweet orange of these hormonal properties. juice and ascorbic acid produced endometrial progestational proliferati\re reactive. In this respect, it possesses a progcsteronc-like activity and may be used alone or in combination with progesterone in all conditions associated with low level of progcsteronc as in habitual and threatened abortions. &er mienturn,has been experimentally proved to produce androgenic activity as it increased the weights of the prostates and seminal vesicles of castrated male rats, and progesterone-like action as it produced progcstational proliferation in the endometrium of ovariectomized rabbits. Catha edule leaves, when fed to animals, also produced progestational prliferation in the endometrium of rabbits resembling that of progesterone. On feeding Egyptian clover to immature rabbits it increased the uterine weights to a considerable extent; this indicates that clover possesses oestrogenic activity. The oxytocic effect of different plant preparations has been investigated in hq on the uterus of animals at various stages of the sex cycle and after Quinine produced strong hormonal treatments. stimulation of the uterine muscle of pregnant rats and ovariectomized animals treated with progesterone. The effect was less marked on the uterus of oestrous rats and of ovcriectomized animals treated with ocstradiol. Quinine also increased the uterine response of the pregnant uterus to the posterior pituitary extract. Cotton root bark extract increased the uterine motility ofthe pregnant uterus and that of ovariectomtzed ammals treated with progesterone, whereas, it inhibited that of oestrous and ovariectomized rats treated with oestradiol. On the other hand, Lupinus termis seed extract produced consistent motor effects on the uterus of all animals whatever the state of the uterus.
hf. ~WWFOUZ and
532 Antitussive Action of Oxolamine (3-Phenyl-5$-Diethylaminoethyl-1:2:4-Oxadiazole). B. SIL~~ESTRI~~ (Italy). (J-phcnyl-5-B-diethylaminoethyla new compound synthetized and studied in the .Angelini Research L,aboratorirs, presents the following properties: (a) an antitussive action (b) an analgesic-anti-inflammatory action of the aspirin-type (c) a spasmolytic action of the papaverine-type Id) a mild antipyretic and local anaesthetic action. The antitussivr action of oxolamine is particularly evident against experimental cough induced by irritating vapours, which produce inflammation and spasm of the bronchial tree. Oxolamine is less active against centrally evoked cough. The possibility is therefore discussed that the antitussive action of oxolamine is taking place through a synergrsm between the mild depressive action on the coughing centre and the anti-inflammatory and spasmolytic properties. Oxolamine
1 ::! :+oxadiazole),
533
The Behaviour of Hypertensive Drugs on the Suprarenal Gland and Kidney Perfusion in the Cat. P. D. GARCIA DE JALON and L. .A. L. SAxros (Spain). The
pharmacological
controls
of
5HT
were