Posted by Sunnely on July 30, 2000, at 19:53:00
In reply to Pagoclone--Cam, Sunnely, or Anyone?, posted by Snowie on July 30, 2000, at 7:39:12
> Anybody hear of Pagoclone, a new drug under development by Interneuron Pharmaceuticals for treating panic disorder and GAD? Any info is appreciated!
>
> SnowieAllow me to share my 2 cents. This info was from a psychopharm newsletter from 1998. It may not be the latest news but I think still newsworthy, nonetheless.
As you have mentioned, pagoclone is a new drug under development by Interneuron Pharmaceuticals, Lexington, Mass, for treating panic disorder and GAD. It works by increasing the function of the major inhibitory neurotransmitter (brain chemical) GABA (gamma aminobutyric acid). Panic disorder is believed to be associated with excessive nerve activity caused by a decrease in GABA function. Pagaclone is a partial agonist at a modulatory site on the GABA receptor, which enhances the action of GABA in the brain. That effect reduces excessive nerve activity associated with anxiety and panic attacks. (Partial agonists are a group of drugs that have a mixture of agonist [pro] and antagonist [against] properties. They act as agonists in the face of neurotransmitter deficiency and antagonists in the face of neurotransmitter excess.)
A two-week pilot study of pagoclone was conducted (a couple years ago) in 16 patients with panic disorder in the U.K. These patients experienced 2 to 10 panic attacks per week in the two weeks prior to enrolment. Patients were randomly assigned to receive either 0.1 mg of pagoclone 3 times daily or placebo for 2 weeks. All patients received placebo during a wash-out period in week 3, and in weeks 4 and 5, patients who had initially received pagoclone received placebo and vice-versa. During week 6, there was a final wash-out period. Outcome measurements included change in the number of full and partial panic attacks, withdrawal, and rebound anxiety symptoms.
Pagoclone produced a significant reduction in the total number of panic attacks (40%) over a two-week period. Patients also experienced a 40% reduction in the number of panic attacks per day compared to the pre-treatment period. There was no significant change in the total number of panic attacks during placebo treatment. Patients did not experience sedation, withdrawal or rebound anxiety effects, which are common with benzodiazepine drugs often used to treat panic disorder.
Investigators concluded that the results of the study provide clinical support for the hypothesis that the administration of pagoclone is of significant benefit in panic disorder. They were encouraged by the rapid onset of action seen among patients in this study as well as by the absence of sedative effects and withdrawal symptoms. They suggested that it might have same speed of onset as drugs such as alprazolam (Xanax) but with fewer problems such as sedation, unsteadiness, and withdrawal.
The director of clinical research at Interneuron Pharmaceuticals indicates that if further pagoclone trials prove promising, it will be superior to treatments for panic disorder such as benzodiazepines, buspirone (BuSpar), and antidepressants. Benzodiazepines can't be used long-term because of their addictive qualities, and buspirone isn't effective in all panic disorder patients. Tricyclic antidepressants have unwanted side effects such as sedation, and selective serotonin reuptake inhibitors (SSRIs) can take time to become effective.
The director of research believes that pagoclone will be indicated for generalized anxiety disorder (GAD), depending on results of further studies. A phase 2/3 dosing study is currently underway to compare the effects of three doses of pagoclone to placebo during a 10-week period in 280 patients. Primary outcome measures will include the frequency of panic attacks experienced by patients. The study is expected to be completed in 1999; approval of the drug in the US could occur as soon as 2000.
poster:Sunnely
thread:41727
URL: http://www.dr-bob.org/babble/20000729/msgs/41790.html