1 Bradykinin-induced increased plasma protein extravasation (IPPE) and blood flow have been assessed in guinea-pig skin by isotopic methods. 2 The effects of a range of adrenoceptor agonists on these parameters have been investigated. 3 a-Adrenoceptor agonists inhibited IPPE and reduced cutaneous blood flow. The potency of a-agonists as inhibitors of IPPE correlated with their vasoconstrictor effects. The actions of noradrenaline on both IPPE and blood flow were blocked by phentolamine but not by propranolol.4 P-Adrenoceptor agonists inhibited IPPE at doses which either increased or caused little change in cutaneous blood flow. Isoprenaline inhibition of IPPE was reduced by propranolol but was unaffected by phentolamine. 5 The inhibitory action of a-agonists on IPPE can be explained by a reduction in blood flow to the affected site. Beta agonist inhibition is not due to effects on blood flow but is probably caused by a reduction in permeability of the microvessels.

I The incorporation of [3H]-thymidine into guinea-pig lymphocytes stimulated by a plant lectin (concanavalin A), soluble antigen (tuberculin (P.P.D.)) and syngeneic hepatoma cells, was partially inhibited (50%) by histamine in vitro. 2 The effect of histamine on both mitogen and antigen dose-response curves suggests a non-competitive, probably physiological antagonism.3 The inhibitory dose range of histamine lay between 10 nm and 30 AM with an ID50 of approximately 400 nM. 4 The potency order for histamine analogues for the inhibition of lymphocyte activation was histamine > 4-methylhistamine > 2-methylhistamine > 3-methylhistamine. This is in accord with the mediation of the response through an H2-receptor. 5 H2-receptor antagonists reversed the inhibitory effect of histamine in a dose-related manner, but both metiamide and burimamide, in high concentrations, augmented lymphocyte activation in their own right. This precluded the determination of affinity constants and made it impossible to state with certainty that the inhibition of lymphocyte activation by histamine was mediated by an H12-receptor.

Five non-steroidal anti-inflammatory drugs (indomethacin, naproxen, meclofenamic acid, feprazone and phenylbutazone: NSAIDs) and three glucocorticosteroids (dexamethasone, hydrocortisone and prednisolone) have been tested as local inhibitors of increased vascular permeability in guinea-pig skin. Lesions were induced by histamine or by antigen to evoke type I (passive cutaneous anaphylaxis), type III (reverse passive Arthus) and type IV (delayed hypersensitivity) allergic reactions. NSAIDs and glucocorticosteroids caused either weak, inconsistent inhibition or slight, high-dose inhibition of the response to histamine. None of the drugs tested showed significant inhibition of the type IV response. The NSAIDs caused dose-related inhibition of both type I and type III responses whereas glucocorticosteroids were ineffective. Maximum inhibition with the NSAIDs was never greater than 50--60% Feprazone, meclofenamic acid and indomethacin were the most potent inhibitors of histamine, PCA and Arthus responses respectively. The possible significance of the effects of these anti-inflammatory agents on vascular permeability is discussed.

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1 The absorption of PRD‐92 Ea, a new anti‐allergy drug, was studied in volunteer subjects. 2 The 14C‐labelled drug was administered orally and the radioactivity measured in plasma, urine and faeces. 3 Mean peak plasma concentration was 3.3 micrograms/ml, with a concentration of over 1 micrograms/ml maintained 4 h after administration. 4 The mean plasma half‐life (T 1/2) was 114 min. 5 The mean percentage recovery in the urine was 9.5%. 6 Oral administration leads to significant and sustained plasma concentrations, and the oral route should be suitable for drug evaluation in clinical practice.