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Biomedical subjects

W Feldberg

Publications and source records attributed to W Feldberg.

At least 37 records · Page 2Linked to original sources
PubMed1977

C-fragment of lipotropin--an endogenous potent analgesic peptide.

1 A series of peptides derived from porcine lipotropin was examined for analgesic and other morphine-like properties on infusion into the cannulated third ventricle of cats.2 Lipotropin (LPH 1-91) itself produced no analgesia or other morphine-like effects when infused in a dose of 150 mug.3 C-fragment (LPH 61-91) produced strong long-lasting analgesia when infused in a dose of 10 or 20 mug; on a molar basis the potency was between 90 and 180 times that of morphine. The following morphine-like effects were also produced: shivering leading to fever, vasodilatation of the pinnae, mydriasis, opening of the palpebral fissures, tachypnoea with bouts of panting, vocalization, hyperexcitability, restlessness and catalepsy. All the effects, including analgesia, were abolished by an intraperitoneal injection of naloxone (1 mg/kg).4 Hyperglycaemia, another central effect produced by morphine, was obtained with C-fragment infused in a dose of 60 mug.5 On intravenous injection, C-fragment produced analgesia with a dose of about 200 mug/kg. Administered by this route, C-fragment was again more potent than morphine.6 C'-fragment (LPH 61-87), LPH 61-78 and LPH 61-69, either had no analgesic effect or produced weak short-lasting analgesia when infused in doses up to 100 mug.7 Methionine enkephalin (LPH 61-65) either produced very weak short-lasting analgesia or had no analgesic effect when infused in doses of between 30 and 400 mug.8N-methyl methionine enkephalin amide in which both termini of methionine enkephalin were protected against degradation by exopeptidases produced long-lasting analgesia when infused in doses of 150 to 180 mug; its analgesic potency was approximately 100 times less than that of C-fragment. Blocking only one terminus of methionine enkephalin did not appear to endow the peptide with analgesic properties. The N-methyl pentapeptide amide produced other morphine-like effects of which the most striking was catalepsy. All the effects were abolished by intraperitoneal naloxone (1 mg/kg).

Analgesics↗
PubMed1976

Possible association of schizophrenia with a disturbance in prostaglandin metabolism: a physiological hypothesis.

Schizophrenia may be associated with increased prostaglandin synthesis in certain parts of the brain. This hypothesis is based on the following findings: (1) Catalepsy, which is the nearest equivalent in animals to human catatonia, develops in cats when prostaglandin E1 is injected into the cerebral ventricles and when during endotoxin or lipid A fever the prostaglandin E2 level in cisternal c.s.f. rises to high levels; however, when fever and prostaglandin level are brought down by non-steroid anti-pyretics which inhibit prostaglandin synthesis, catalepsy disappears as well. (2) Febrile episodes are a genuine syndrome of schizophrenia.

Animals↗
PubMed1976

Analgesia produced by morphine when acting from the liquor space.

1 In cats analgesia was produced by morphine sulphate introduced into different parts of the liquor space in doses too small to be effective on intravenous injection. Analgesia was measured with the tail pinch method of Russell & Tate (1975). 2 On infusion into the fourth ventricle or into the subarachnoid space beneath the ventral surface of the brain stem caudal to the pons, doses of 100 to 200 mug of morphine sulphate were sufficient to produce strong long-lasting analgesia. On injection into the cisterna magna somewhat larger doses (400 to 800mug) were required. 3 It is concluded that the site where morphine acts when producing analgesia in all three circumstances is at the ventral surface of the brain stem. 4 The possibility is discussed that the structures acted upon are tryptaminergic nerve fibres. They arise from the raphe nuclei, belong to a descending inhibitory pathway, and on their way to the spinal cord, reach the ventral surface of the brain stem lateral to each pyramid, where they could be reached and acted upon by the morphine. This theory postulates a morphine sensitivity of tryptaminergic nerve fibres.

Analgesics, Opioid↗
PubMed1976

Vasodepressor effects obtained by drugs acting on the ventral surface of the brain stem.

1. In cats anaesthetized with I.P. pentobarbitone sodium and atropinized with intravenous atropine methyl nitrate, the effects on arterial blood pressure were examined of nicotine, physostigmine, carbachol, glycine and pentobarbitone sodium applied to the exposed ventral surface of the brain stem by means of paired Perspex rings placed across the medulla. The drugs were placed inside each ring in a volume of 10mul. 2. Nicotine (0-5-6mg/ml.) produced a fall in blood pressure when the upper limit of the areas covered by the rings was about 5-6 mm caudal, but not when it was just caudal to the trapezoid bodies. The depressor effect was obtained both on bilateral and unilateral application. After application the nicotine sensitive area became for several minutes insensitive to its renewed application. 3. The depressor effect of nicotine was sensitive to hexamethonium (50 mg/ml.) but resistant to atropine (50 mg/ml.) similarly applied. 4. When the nicotine sensitive areas had become insensitive to nicotine, bilateral carotid occulusion produced its normal sustained pressor response. 5. By applying the nicotine through a single Perspex ring which could be moved stepwise along and across the medulla, the nicotine sensitive area was localized and the highest sensitivity was found in a region around and a little caudal to the rootlets of the XIIth cranial nerve. 6. Physostigmine (25 and 50 mg/ml.) and carbachol (6 mg/ml.) produced a fall in blood pressure when the uppermost limits of the areas covered by the paired rings were 5-6 mm caudal to and also when they were just caudal to the trapezoid bodies. From both regions the effects were obtained on bilateral and unilateral application. Their depressor effects were sensitive to atropine but resistant to hexamethonium similarly applied. 7. Glycine (200 mg/ml.) and pentobarbitone sodium (100 mg/ml.) produced scarcely any blood pressure effects when applied bilaterally to the nicotine sensitive areas but produced strong depressor effects on more rostral application, i.e. when the uppermost limit of the areas covered by the rings were just caudal to the trapezoid bodies. 8. It is concluded that the ventral surface of the medulla contains at least two bilateral areas from which vasodepressor effects are obtained on topical application of drugs: a more caudally situated one which is sensitive to nicotine, but insensitive to glycine and pentobarbitone sodium; a more rostrally situated one which is insensitive to nicotine but sensitive to glycine and pentobarbitone sodium; and both areas are sensitive to carbachol and physostigmine.

Animals↗
PubMed1975

Hyperglycaemia produced by drugs with analgesic properties introduced into the cerebral ventricles of cats.

1 The effects on blood glucose of four substances with analgesic properties (apomorphine, pethidine, codeine and etorphine) and of prostaglandin E(1) were examined in unanaesthetized cats. They were applied by the intraventricular route being either injected into a lateral ventricle or infused into the fourth ventricle through implanted Collison cannulae.2 Apomorphine gave rise to pronounced hyperglycaemia in a dose of 0.75 mg which produced scarcely any hyperglycaemia on intravenous injection. It was more effective on infusion into the fourth ventricle than on injection into a lateral ventricle and was approximately half as potent as morphine in provoking hyperglycaemia.3 Codeine produced no hyperglycaemia in doses of 0.75 and 1.5 mg.4 Pethidine had a weak hyperglycaemic action in doses of 0.75 and 1.5 mg, but the effect was not regularly obtained. Potency of the drug was at most only a third to a sixth that of morphine.5 Etorphine produced strong hyperglycaemia on infusion into the fourth ventricle in a dose of 10 mug. Unlike apomorphine or morphine it was more potent on injection into a lateral ventricle when it produced a strong hyperglycaemic response in doses of 5 or 1 mug, which were subthreshold on infusion into the fourth ventricle. However, this response may have been brought about indirectly as a result of severe asphyxia and of convulsions associated with the injections. On infusion into the fourth ventricle, etorphine was about 75 times as potent as morphine in producing hyperglycaemia.6 Prostaglandin E(1) had no hyperglycaemic action when infused into the fourth ventricle in a dose of 400 ng.

Analgesics↗
PubMed1975

Vasopressin release by nicotine: the site of action.

1. In cats anaesthetized with chloralose the release of neurohypophysial hormones was examined after injection of nicotine into the cerebral ventricles or cisterna magna or its topical application through perspex rings to the ventral surface of the brain stem. The release was measured by assaying the hormones in samples of venous blood. 2. Injected into a lateral or the third cerebral ventricle, nicotine (0.5 to 1 mg) produced release of vasopressin without oxytocin. When the aqueduct was cannulated, preventing access to the fourth ventricle and to the subarachnoid space, this release did not occur. 3. Vasopressin was also released without oxytocin when nicotine (0.25 to 2 mg) was injected into the subarachnoid space through the cisterna magna. With this route of administration the nicotine did not enter any part of the ventricular system. 4. Applied through paired perspex rings placed across the ventral surface of the brain stem, nicotine again produced release of vasopressin without ocytocin. The amount of nicotine placed in each ring was usually 80 mug, but a release was obtained with 10 mug and in one experiment with as little as 5 mug. 5. The bilateral region on the ventral surface of the brain stem where nicotine acts when producing release of vasopressin lies lateral to the pyramids and in a longitudinal direction, 6 to 9 mm caudal to the trapezoid bodies. 6. The vasopressin release by nicotine injected intraventricularly or intracisternally, or applied topically to the ventral surface of the brain stem was not due to absorption of nicotine into the blood stream, nor to blood pressure effects. 7. It is concluded that nicotine acts on the ventral surface of the brain stem probably by activating the central projection to the supra-optic and possibly also the paraventricular nuclei of afferent pathways in the sinus and vagus nerves which control the release of vasopressin in response to changes in blood volume or distribution.

Administration, Topical↗
PubMed1975

Comparison of the hyperglycaemic effect of adrenaline and morphine introduced into the liquor space.

1. In unanaesthetized cats a comparison is made of the hyperglycaemic effects of adrenaline and morphine, when injected or infused through chronically implanted cannulae, into different regions of the cerebral ventricles or of the subarachnoid space, in order to determine their sites of action. 2. On injection into the cerebral ventricles both adrenaline and morphine have to reach the subarachnoid space beneath the ventral surface of the brain stem before they can exert their hyperglycaemic effect. The adrenaline has to reach the region rostral to the pons, i.e. the fossa interpeduncularis, and the morphine the region caudal to the trapezoid bodies. These conclusions are based on the following findings. 3. When adrenaline (55 mug) and morphine (0-75mg) were infused into one or other of these two regions, adrenaline produced strong hyperglycaemia on infusion into the fossa interpeduncularis, but had scarcely any hyperglycaemic effect on infusion into the region caudal to the trapezoid bodies. The reverse result was obtained with morphine. 4. It is concluded that the adrenaline hyperglycaemia is mainly a peripheral effect. It occurs after the adrenaline has been absorbed into the blood stream from the fossa interpeduncularis but an additional central component, an action on brain stem structures reached from the fossa interpeduncularis, cannot be excluded. The morphine hyperglycaemia is a central effect due to an action on superficial structures of the ventral surface of the medulla oblongata, caudal to the trapezoid bodies.

Animals↗
PubMed1975

Prostaglandins, endotoxin and lipid A on body temperature in rats.

1. In unanaesthetized restrained rats kept at an ambient temperature of 21-23degrees C, rectal temperature was continuously monitored and the temperature effects of injections of prostaglandins, endotoxin from Salmonella abortus equi, lipid A, and antipyretics were examined. 2. Fever occurred when prostaglandin E1, E2, F1alpha or F2alpha (PGE1, PGE2, PGF1alpha, PGF2alpha) was injected into the cerebral ventricles in doses of 200 ng and 2 mug. PGE2 was the most potent prostaglandin followed in descending order by PGE1, PGF2alpha, and PGF1alpha. The fever produced by 2 mug of PGE1 and PGE2 was short and followed by a fall in temperature to below the pre-injection level. 3. I.V. injections of endotoxin and lipid A in doses of 3 or 10 mug usually caused a long lasting fall in temperature, but when injected into the cerebral ventricles in doses of 400 ng or 1 mug, they produced long lasting fevers. 4. Injected I.V. or I.P., indomethacin and paracetamol had a hypothermic action of their own. Indomethacin was more potent than paracetamol and both were more potent than injected I.P. 5. I.V. and I.P. injections of indomethacin and paracetamol did not reverse the hypothermia in response to I.V. endotoxin or lipid A, but the fever responses to their injection into the cerebral ventricles were prevented and abolished by the antipyretics. 6. It is concluded that in rats endotoxin and lipid A, or the endogenous pyrogens produced by them, do not readily pass through the blood-brain barrier into the brain tissue. If they do reach brain tissue, as when injected into the cerebral ventricles, they stimulate synthesis and release of prostaglandin in rats as they do in other species, and thereby produce fever. The hypothermia in response to I.V. endotoxin or lipid A, on the other hand, is thought to be independent of prostaglandin synthesis and to result from a direct toxic action on the skin vessels.

Acetaminophen↗