Electric recording with insulated steel electrodes in the dorsal part of the medulla of the cat has revealed an area which responds to changes in the tonicity of the blood stream. Hypertonic saline solutions injected intravenously resulted in a response characterized by increased electrical activity in the floor of the fourth ventricle at the level of the obex. The region involved is in juxtaposition to the area postrema overlying the vagal nuclei and may represent a central site of osmoreception.

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The present study was undertaken to compare intravenous methohexitone, given as an adjunct to the behaviour therapy of phobias, with another centrally-acting, rapidly metabolised intravenous agent, propanidid, and also with normal saline. Thirty-five patients were included in the trial, all of whom had had phobic symptoms of at least one year's duration which were seriously interfering with their lives — 15 had specific phobias, 9 had social phobias and 11 had agoraphobia. Treatment consisted of twelve weekly drug-assisted desensitization treatments, using either 1 per cent methohexitone, 2.5 per cent propanidid or normal saline. Within each diagnostic group the drugs were randomly allocated. All treatments were conducted by one of the authors and all assessments by the other (who did not know which of the three preparations the patient had received). In addition to monthly ratings of the phobic symptoms, assessments of anxiety and depression were made, using self-rating scales. Patients were followed up six months after the end of treatment. Patients with specific phobias fared best, 9 out of the 13 who completed being considered to be markedly improved. Although the numbers are small there was a suggestion that patients receiving the two active drugs did better than those on the placebo. While methohexitone and propanidid were similarly effective, recovery time was much more rapid with propanidid. No patient in the specific phobia group relapsed significantly during the six months follow-up period. Furthermore, as the phobia improved the general anxiety level fell. Few depressive symptoms arose during successful desensitization, and there was no evidence of symptom substitution. Patients with social phobias and agoraphobia did far less well. In neither case did the active drugs appear to possess any advantage over placebo. Furthermore, of the 7 patients with agoraphobia who had improved, 4 relapsed within six months. It was concluded that drug-assisted desensitization is likely to be of greatest benefit in the management of specific phobias, with propanidid being the drug of choice.