Various nitrogen analogs of delta6a,10a-tetrahydrocannabinol were synthesized by a general procedure described in an earlier communication. Minimum effective doses (MED50's) and lethal doses (LD50's) were determined by a modified Irwin mouse screen after iv administration of compounds in PEG 200. The most potent compounds were the propargyl (5t), allyl (5m), and chloroallyl (5o-q) derivatives. Overt behavioral effects (CNS depression, static ataxia, and hypersensitivity) of 5t and Roger Adams' carbocyclic analog (III) were found to be similar in the mouse, cat, dog, and monkey. Dichloroisoproterenol prevented and reversed many of the depressant effects of both III and 5t but had no effect on the ataxia produced by these compounds. In antinociceptive tests, 5t was active in the phenylquinone and Eddy hot-plate tests but was inactive in the tail-flick test.

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At least half the hyperglycemic response (in hepatic venous blood) to intravenous epinephrine was found to be dependent on the integrity of the medulla oblongata caudal to the cerebellar peduncles. Transection of the medulla at the level of the fovea inferior unmasked a vagus-mediated hypoglycemic response to epinephrine. Changes in blood glucose concentration after epinephrine administration were independent of blood pressure and the base-line blood glucose levels. Microinjections of epinephrine into the floor of the fourth ventricle initiated an immediate hyperglycemic response without affecting blood pressure. It is concluded that only half the hyperglycemic response to epinephrine is due to direct peripheral action of epinephrine. The balance of the response is initiated by epinephrine-sensitive receptors in a hyperglycemic center in the floor of the fourth ventricle.

The sizes of passive cutaneous anaphylaxis (PCA) reactions, mediated by reagin or hyperimmune antibodies, were directly related to the degree of sensitization and, to a lesser degree, to the dose of the challenging antigen. Inhibition by anti-anaphylactic drugs of both types of PCA was inversely related to the degree of sensitization. Anti-anaphylactic drugs shifted the diameter-antibody concentration slopes to the region of higher antibody concentration in a parallel manner which suggests a possible competitive nature of the inhibitory mechanisms of these drugs. Disodium cromoglycate and methysergide were effective against reagin-mediated PCA but they were ineffective against hyperimmune antibody-mediated PCA. Then-yldiamine and chlorpheniramine had marginal activities against both PCA systems. Aminophylline was effective against both systems and it had similar potencies and efficacies against both types of PCA. Three β-adrenergic sympathomimetic drugs were more efficacious against hyperimmune antibody-mediated PCA than against reagin-mediated PCA.

1 The ubiquitous actions of the cyclo‐oxygenase inhibitors are described. 2 These include the inhibitory effect on prostaglandin synthesis and the direct effect of aspirin on lymphocytes and their ability to produce lymphokines. 3 Aspirin reduces some types of platelet aggregation possibly involving inhibition of the precursors of thromboxane A2 and prostacyclin. 4 The therapeutic implications in relation to transient ischaemic attacks, coronary artery disease and reno‐allograft rejection are discussed. 5 The beneficial and adverse effects on the gastro‐intestinal tract are described. 6 The effects of aspirin‐like drugs on the genito‐urinary tract are described with particular reference to their adverse effects on labour and their therapeutic effect on dysmenorrhoea.