A pilot study of the short-term psychotropic effects of GPA 2640.

Thirty-two anxious nonpsychotic inpatients participated in a four-day, double-blind repeat crossover study of a new drug, GPA 2640, and placebo. Each treatment period lasted for one day, and the study lasted for four days. Twenty patients completed the study, and 28 completed two or three days. The doses were individually adjusted and mostly ranged between 1100 and 1300 mg daily. Several valid observer-rating and self-rating scales were used. There was a slight trend for GPA 2640 to yield somewhat lower anxiety scores on drug days than on placebo days, but none of the differences between rating and self-rating scores reached a significant level. A few patients reported a marked improvement in mood after two to four days, but the significance of this finding cannot be evaluated from this design. Two patients developed temporary paranoid delusions which may have been drug related. Two patients had raised SGOT levels after the study. There were no significant differences in vital signs between drug days and placebo days. The results signify that the drug has no immediate antianxiety effects (such as have been demonstrated with benzodiazepines in two previous studies utilizing the same design). This does not preclude the possibility of delayed anxiolytic effects or of other delayed psychotropic effects such as can be observed with antipsychotic drugs or antidepressants.

The effects of one-day treatment of anxiety with high doses of halazepam.

The main purposes of this study were to examine the effects of one-day treatment of anxiety and to test whether significant relief of anxiety can be achieved in a short time period by frequency individual adjustment of doses. A double-blind crossover study of halazepam and placebo was carried out with 22 patients, 20 completing the study. Each treatment lasted for one day. Oral medication was administered starting with a dose of 40 mg and the dose adjusted every 2 hours. The total daily dose did not exceed 600 mg. Several rating and self-rating scales were used. All observer rating scales and several self-rating scales discriminated at a significant level. The design appeart to be suitable for the rapid screening for anti-anxiety properties of new drugs.

Subsensitivity of beta responses during therapy with a long-acting beta-2 preparation.

The question whether some tolerance or subsensitivity of various beta receptors develops during therapy with long-acting oral beta-2 agents has practical and theoretical importance. We applied a strong beta-2 stimulus (terbutaline, 5.0 mg orally) at weekly intervals for up to three weeks in 19 stable asthmatics and bronchitics while commencing 5.0 mg terbutaline three times daily. The evening dose was omitted before each morning challenge. Challenges were continued at one and two weeks off terbutaline in some patients to test return of beta function. Patients received no ephedrine for two weeks before the study but were allowed aminophylline or isoproterenol inhalations up to 18 and 4 hr before challenges, respectively. Pulmonary function, pulse, and blood pressure were monitored at 0, 60, 120, and 180 min, and metabolic parameters measured at 0 and 180 min. There was significant drug tolerance in the drop and minimum diastolic pressure reached, rise in lactate, cyclic AMP, and blood glucose, and drop in eosinophils. Peak FEV1 and V50 dropped slightly, but vital capacity and minimal airway resistance did not change significantly. During continuous therapy this slight bronchial subsensitivity is probably obscured by elevated baseline function. It might assume importance during periods of excessive inhaler use or abrupt drug withdrawal.