Models of arthritis and the search for anti-arthritic drugs.

Introduction. Scope of the Work. Guidelines for Research with Animals. Moral and Ethical Considerations. Principles and Training Programs. Design of Candidate Radiopharmaceuticals. Identification of Clinical Need. Choice of Radionuclide. Screening Studies. Drug Development. Concept of Biological Models. In vitro Models. Choice of Biological Models. Species Variations. Transgenic Mice. Dogs and Kangaroos. Poison Arrow Frog. Giraffe. Tomographic Physiological Chemistry. ARG. SPET. PET. SIMS. Keyword Guide to Selection of Biological Models. References. Glossary of Abbreviations.

Biological Models in Radiopharmaceutical Development

Methods and devices for maintaining a desired therapeutic drug effect over a prolonged therapy period are provided. In particular, oral dosage forms that release drug within the gastrointestinal tract at an ascending release rate over an extended time period are provided. The dosage forms may additionally comprise an immediate-release dose of drug.

Methods and devices for providing prolonged drug therapy

A device for delivering a drug by inhalation is disclosed. The device includes a body defining an interior flow-through chamber having upstream and downstream chamber openings, and a drug supply unit contained within the chamber for producing, upon actuation, a heated drug vapor in a condensation region of the chamber. Gas drawn through the chamber region at a selected gas-flow rate is effective to form drug condensation particles from the drug vapor having a selected MMAD between 0.02 and 0.1 MMAD or between 1 and 3.5 gm. A gas-flow control valve disposed upstream of the unit functions to limit gas-flow rate through the condensation region to the selected gas-flow rate. An actuation switch in the device activates the drug-supply unit, such that the drug-supply unit can be controlled to produce vapor when the gas-flow rate through the chamber is at the selected flow rate.

Inhalation device for producing a drug aerosol

Devices and methods of entraining a substance within an airflow are disclosed. Condensation aerosol delivery devices and methods of consistently producing multiple doses of a substance, such as a drug, having high purity, high yield, characterized by a particle size distribution appropriate for pulmonary delivery, and which can be administered to a user in a single dose are also disclosed.

Multiple dose condensation aerosol devices and methods of forming condensation aerosols

The prostaglandins PGE 1 and PGE 2 and isoproterenol were effective bronchodilators capable of reversing the increased airway resistance and decreased airway compliance induced by cholinergic stimulation in the cat. Administration of the prostaglandins by serosol greatly increased their potency compared with the i.v. route, whereas the converse was true of isoproterenol. Cardiovascular effects of PGE 1 and PGE 2 were prominent only after i.v. administration. Blockade of various neurologic pathways failed to affect the bronchodilating properties of PGE 2 . When administered by aerosol, the prostaglandins represent a new and novel class of potent bronchodilator agents.

Bronchodilator activity of the prostaglandins E 1 and E 2 .

The use of quaternary salts of promethazine by the inhalation route is described. The thus administered compositions provide new, non-toxic, potent means for relieving bronchial spasm and bronchoconstriction in warm-blooded animals.

Inhalation therapy for relieving bronchial spasm using quaternary salts of promethazine

Cycloleucine (1-aminocyclopentane carboxylic acid) was shown to be quite active in preventing the clinical and histologic signs of experimental allergic encephalomyelitis and adjuvant arthritis. In contrast, it was inactive in two in vitro models designed to detect various types of clinically effective anti-inflammatory, anti-immune agents: tissue culture growth and polymorphonuclear leukocyte migration. Its immunopharmacologic spectrum differs from that of other clinically active agents, suggesting that it may work via a different mechanism or at a different site.

Immunopharmacologic effects of cycloleucine.

Acute tolerance developed to an infusion of norepinephrine given over a 3-hour period to normal anesthetized dogs. Neither splenectomy nor adrenalectomy altered the development of tolerance. Hemoconcentration, acidosis, decreased blood volume and decreased cardiac output accompanied the development of tolerance. Administration of plasma expanders at the height of tolerance temporarily restored normal sensitivity to norepinephrine but did not affect the acidosis. Adjustment of blood pH to normal with THAM buffer or sodium bicarbonate did not affect tolerance. Experiments designed to demonstrate if neural circulatory adjustments could explain tolerance to norepinephrine were negative. These included the administration of hexamethonium and atropine and decerebration and spinal cord section. No evidence was found for increased removal or destruction of norepinephrine. At the height of tolerance, the norepinephrine levels were very high. Liver monoamine oxidase activity was not enhanced and monoamine oxidase inhibited animals showed the same degree of acute tolerance.

Marvin E. Rosenthale

Papers

Bronchodilator activity of the prostaglandins E 1 and E 2 .

Inhalation therapy for relieving bronchial spasm using quaternary salts of promethazine

Immunopharmacologic effects of cycloleucine.

Acute tolerance to norepinephrine in dogs

Bronchodilator and antiallergic effects of thiazinamium chloride in guinea pigs, rats, cats and dogs.