On the nature of the chemical mediators involved in anaphylactic reactions in mice. (41/224)

The effects of mepyramine, promethazine, chlorpromazine and lysergic acid diethylamide have been compared on the capillary permeability changes of the skin, produced by histamine, by 5-hydroxytryptamine and by passive cutaneous anaphylaxis in mice. Promethazine, mepyramine and chlorpromazine can inhibit, in decreasing order of activity, the effect of histamine, whilst lysergic acid diethylamide is inactive. Lysergic acid diethylamide and chlorpromazine are equally potent inhibitors of the action of 5-hydroxytryptamine on the peripheral vascular bed, whilst mepyramine is inactive. Promethazine has intermediate activity. Passive cutaneous anaphylaxis is strongly inhibited by chlorpromazine and by promethazine. Mepyramine and lysergic acid diethylamide, each injected alone, affect only weakly the anaphylactic reaction. However, passive cutaneous anaphylaxis is almost completely abolished by the simultaneous injection of the two last antagonists. It is suggested that the anaphylactic reaction in mice is the result of simultaneous release of both mediators, histamine and 5-hydroxytryptamine, each of them strengthening the effect of the other.  (+info)

Actions of derivatives of lysergic acid on the heart of Venus mercenaria. (42/224)

5-Hydroxytryptamine and a number of (+)-lysergic acid derivatives have been tested on the heart of Venus mercenaria. One group of derivatives was found to increase the amplitude and frequency of heart beat in a manner much like 5-hydroxytryptamine. It included the monoethylamide, diethylamide, propanolamide (ergometrine), butanolamide (methylergometrine) and certain peptide derivatives of lysergic acid without substituents in positions 1 or 2. Of these, lysergic acid diethylamide was the most active. Given sufficient time (up to 4 hr), as little as 10 ml. of 10(-16) M lysergic acid diethylamide produced a maximum increase in amplitude and frequency in about one-half of the 80 hearts on which it was tested. Its action was very slowly reversed by washing, as was true of all lysergic acid derivatives. A second group of lysergic acid derivatives, substituted in positions 1 or 2, had weak excitor action, if any, and specific 5-hydroxytryptamine blocking action. This group consisted of 1-methyl-, 1-acetyl-, and 2-bromo-lysergic acid diethylamide and 1-methyllysergic acid butanolamide (methysergide). Of these, the last showed least signs of excitor action, usually none up to 10(-4) M, and it blocked 5-hydroxytryptamine in a molar ratio of about one to one.  (+info)

Actions of certain amines on cerebral cortical neurones. (43/224)

A number of derivatives of tryptamine and phenethylamine, and certain other compounds, were tested on neurones in the cerebral cortex of cats by iontophoretic release from micro-pipettes. The characteristic action of many of these compounds was a depression of the neuronal discharge initiated by synaptic activity or by the application of L-glutamate; imidazolylacetic acid, dopamine, ephedrine and ergometrine were particularly effective. Catechol amines, hydroxytryptamines and imidazolylacetic acid had a relatively quick and rapidly reversible action, not unlike that of gamma-aminobutyric acid, whereas ephedrine and derivatives of lysergic acid diethylamide caused a slower and more prolonged depression of the amplitude of spikes, rather like atropine. Several compounds, including 5-hydroxytryptamine, adrenaline and ergometrine, could also excite the same neurone when larger amounts were applied. A few substances, such as dopa and methylergometrine, had a predominantly excitant action.  (+info)

REMOVAL OF INTERFERING NUCLEOTIDES FROM BRAIN EXTRACTS CONTAINING SUBSTANCE P. EFFECT OF DRUGS ON BRAIN CONCENTRATIONS OF SUBSTANCE P. (44/224)

Several methods for removing interfering nucleotides, adenosine-5'-monophosphate and adenosine 5'-triphosphate from brain extracts have been studied. An enzymic method, using adenylic acid deaminase, has been found suitable. This deaminates adenosine monophosphate to 5'-inosinic acid, an inactive compound which does not influence the estimations of substance P. Owing to the adenosine triphosphatase content of the enzyme extract, adenosine triphosphate was also inactivated. For the estimation of adenosine monophosphate-deaminase activity, a simple colorimetric method is described which measures the ammonia liberated from adenosine monophosphate. Substance P in mouse brain extracts was estimated after treatment of the animals with various drugs, and after the enzymic removal of interfering nucleotides from the brain extracts. The drugs had no effect on the substance P content of mouse brain. The effect of drugs on the contractions of the guinea-pig ileum induced by substance P was also investigated, and the effect of drugs on the estimations of substance P in brain extracts is discussed.  (+info)

STUDIES ON THE LOCALIZATION OF CIRCULATING ANTIGEN-ANTIBODY COMPLEXES AND OTHER MACROMOLECULES IN VESSELS. II. PATHOGENETIC AND PHARMACODYNAMIC STUDIES. (45/224)

Localization of circulating antigen-antibody complexes in vessels of guinea pigs by means of anaphylactic shock was found to be mediated by histamine that was released at the time of anaphylaxis. The source of the histamine may have been the mast cell as noted in studies employing a direct attack on the mast cells by octylamine. Platelets played apparently little to no role in guinea pigs in the anaphylactic deposition of circulating complexes. Rat anaphylatoxin was found to cause vascular localization and symptoms of anaphylaxis identical with that brought about by antigen-antibody anaphylaxis. This also was found to be dependent upon the release of histamine. Antibody against Forssman antigen in the vessel walls of the guinea pigs also led to deposition of circulating complexes. This was found not to be histamine dependent. The possible role of local increase in vascular permeability in certain experimental disease states in the localization of circulating complexes is discussed.  (+info)

THE SITE OF THE 5-HYDROXYTRYPTAMINE RECEPTOR ON THE INTRAMURAL NERVOUS PLEXUS OF THE GUINEA-PIG ISOLATED ILEUM. (46/224)

Dose/response measurements were made on the guinea-pig isolated ileum with six agonists, acetylcholine, 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium, choline phenyl ether and histamine. The dose effects were repeated in the presence of each of twelve antagonists and one anticholinesterase. Acetylcholine and histamine were chosen because of their direct mode of action on smooth muscle, nicotine, dimethylphenylpiperazinium and choline phenyl ether were used as examples of drugs that act at the ganglionic acetylcholine receptor. 5-Hydroxytryptamine was the drug investigated. Hyoscine blocked the contractions caused by acetylcholine, 5-hydroxytryptamine and the ganglion-stimulants but left the responses to histamine unchanged. The anticholinesterase N,N'-diisopropylphosphorodiamidic fluoride (mipafox) potentiated all the agonists except histamine. The strength of potentiation decreased in the order 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether, and acetylcholine. The local anaesthetic procaine inhibited to the same extent contractions elicited by 5-hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether. These results showed that 5-hydroxytryptamine, like nicotine, choline phenyl ether and dimethylphenylpiperazinium, mediated its response through the nervous plexus. Of those tested 5-hydroxytryptamine was the only specific antagonist to 5-hydroxytryptamine; lysergic acid derivatives produced spasm and prolonged changes in tone; phenoxybenzamine caused non-specific block. The diverse modes of action of a number of ganglion-blocking agents were selectively used. Thus hexamethonium, pentolinium, and nicotine in its competitive phase, blocked contractions due to nicotine, dimethylphenylpiperazinium and choline phenyl ether and left those due to 5-hydroxytryptamine, acetylcholine and histamine unchanged. The depolarizing ganglion-blocking agents, dimethylphenylpiperazinium and nicotine, inhibited the responses to all the indirectly acting drugs. Furthermore, mecamylamine, a drug with a less well-defined mode of action, partially inhibited contractions due to 5-hydroxytryptamine in a concentration that blocked those due to nicotine, dimethylphenylpiperazinium and choline phenyl ether. Pempidine, known to act like mecamylamine, did not antagonize 5-hydroxytryptamine. It is concluded that 5-hydroxytryptamine activates specific receptors sited at the intramural parasympathetic ganglion cells.  (+info)

EFFECTS OF CHLORPROMAZINE AND BROMOLYSERGIC ACID DIETHYLAMIDE ON GASTRIC SECRETION OF ACID INDUCED BY HISTAMINE IN RATS. (47/224)

In anaesthetized rats in which the lumen of the stomach was perfused with 0.001 to 0.00025 N-sodium hydroxide solution and the pH of effluent fluid was recorded continuously, intravenous administration of chlorpromazine caused transient inhibition of acid secretion. After acid secretion had returned to the control level the responses to histamine were greater than those before chlorpromazine was given. Aminoguanidine, iproniazid and bromolysergic acid diethylamide also potentiated the effect of histamine on acid secretion but the initial inhibition was absent. Indirect evidence from experiments in which mixtures of aminoguanidine with chlorpromazine or bromolysergic acid diethylamide and of iproniazid with chlorpromazine or bromolysergic acid diethylamide were given, suggests that chlorpromazine and bromolysergic acid diethylamide enhance responses to histamine by inhibition of imidazole-N-methyl transferase.  (+info)

THE USE OF LYSERGIC ACID DIETHYLAMIDE (LSD) IN PSYCHOTHERAPY. (48/224)

One hundred of 150 patients with non-psychotic functional psychiatric disorders were benefited by the use of LSD psychotherapy. The dosage of LSD employed was 25 to 2000 micrograms intramuscularly per session for from one to 10 sessions. On this regimen four patients became psychotic and required electroconvulsive therapy. None were permanently harmed.Indications for and contraindications to this form of treatment and a procedure involving a doctor and a nurse as co-therapists are discussed. In particular, LSD is considered to permit "perceptualization of the transference".LSD possibly extends the scope and value of the psychotherapeutic approach in such cases.  (+info)