Research and Clinical Trials on Alprazolam (Xanax)

By Dr Greg Mulhauser
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This list of current clinical research trials on Alprazolam (Xanax) is followed by a short set of abstracts from the most recent research articles published on the drug.

Article Contents

Alprazolam (Xanax) Clinical Research Trials

From our searchable database at ClinicalTrialsFeeds.org, this list includes all the latest information about clinical trials involving Alprazolam (Xanax).

 

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Current Research Literature on Alprazolam (Xanax)

Here are abstracts for some of the latest research articles to have appeared on Alprazolam (Xanax):

Does oral alprazolam affect ventilation? A randomised, double-blind, placebo-controlled trial.

J Psychopharmacol. 2008 Jun 18;
Carraro GE, Russi EW, Buechi S, Bloch KE
Abstract The respiratory effects of benzodiazepines have been controversial. This investigation aimed to study the effects of oral alprazolam on ventilation. In a randomised, double-blind cross-over protocol, 20 healthy men ingested 1 mg of alprazolam or placebo in random order, 1 week apart. Ventilation was unobtrusively monitored by inductance plethysmography along with end-tidal PCO2 and pulse oximetry 60-160 min after drug intake. Subjects were encouraged to keep eyes open. Meanï¿(1/2)+/- was similar (6.21 +/- 0.71 vs 6.41 +/- 1.12 L/min, P = NS). End-tidal PCO2 and oxygen saturation did also not differ between treatments. However, coefficients of variation of minute ventilation after alprazolam exceeded those after placebo (43 +/- 23% vs 31 +/- 13%, P < 0.05). More encouragements to keep eyes open were required after alprazolam than after placebo (5.2 +/- 5.7 vs 1.3 +/- 2.3 calls, P < 0.05). In a multiple regression analysis, higher coefficients of variation of minute ventilation after alprazolam were related to a greater number of calls. Oral alprazolam in a mildly sedative dose has no clinically relevant effect on ventilation in healthy, awake men. The increased variability of ventilation on alprazolam seems related to vigilance fluctuations rather than to a direct drug effect on ventilation.

A comparison of the effects of a subtype selective and non-selective benzodiazepine receptor agonist in two CO2 models of experimental human anxiety.

J Psychopharmacol. 2008 Jun 18;
Bailey JE, Papadopoulos A, Seddon K, Nutt DJ
Abstract Studies in human volunteers that can demonstrate proof of concept are attractive in that possible mechanisms and potential new drug treatments can be examined. We have been developing models of anxiety disorders using the inhalation of 7.5% CO2 for 20 min to model generalised anxiety disorder, as well as using the previously reported 35% CO2 as a model for panic anxiety. In a double-blind, placebo-controlled, three-way crossover study in 12 healthy volunteer subjects, we compared a full agonist at the benzodiazepine receptor that binds to four alpha-subtypes of the receptor (alpha-1,-2,-3,-5) (alprazolam 1 mg), with zolpidem (5 mg), an agonist selective for the alpha-1 subtype of the gamma amino butyric acid-receptor subtype A (GABA-A) receptor, which is a widely used hypnotic drug. Compared with placebo, both drugs significantly attenuated peak CO2-induced changes in subjective feelings after the inhalation of 7.5% CO2 for 20 min. However, there were fewer significant differences after a single vital capacity inhalation of 35% CO2, where zolpidem was less efficacious than alprazolam at reducing CO2-induced symptoms. In conclusion, our results show that zolpidem shows some anxiolytic efficacy in the 7.5% CO2 model, similar to alprazolam, and this is the first report of such an effect of zolpidem in a model of anxiety. These and other studies of benzodiazepines in clinical and volunteer studies suggest a definite role of the GABA-A receptor in CO2-induced anxiety, and it would be of interest to examine other GABA-A receptor subtype selective drugs, which are now in early phase clinical studies and are showing selective efficacy in pharmacodynamic studies.

Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

PLoS ONE. 2008; 3(6): e2337
Agarwal V, Kommaddi RP, Valli K, Ryder D, Hyde TM, Kleinman JE, Strobel HW, Ravindranath V
Cytochrome P450 (P450) is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP) in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP) is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP) while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

Drug screening of hair by liquid chromatography-tandem mass spectrometry.

J Anal Toxicol. 2008 Jun; 32(5): 364-72
Hegstad S, Khiabani HZ, Kristoffersen L, Kunøe N, Lobmaier PP, Christophersen AS
Hair has become an important matrix for drug analysis, complementary to blood and urine as a matrix. A prolonged detection window makes hair analysis suitable for the detection of exposure to illegal and medicinal drugs for periods up to 12 months. In the present study, a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for drug screening in hair was developed and validated. To 20 mg of hair, 0.45 mL of acetonitrile/25 mM formic acid (5:95 v/v) and 50 microL of deuterated internal standards were added, and the sample was incubated in a water bath at 37 degrees C for 18 h. LC separation was achieved with a Zorbax SB-Phenyl column (2.1 x 100 mm, 3.5-microm particle). Mass detection was performed by positive ion mode electrospray LC-MS-MS and included the following drugs/metabolites: nicotine, cotinine, morphine, 6-monoacetylmorphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymeth-amphetamine, cocaine, benzoylecgonine, 7-aminonitrazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, oxazepam, diazepam, alprazolam, zopiclone, zolpidem, carisoprodol, meprobamate, buprenorphine, and methadone. Within- and between-assay relative standard deviations varied from 2.0% to 12% and 2.7% to 15%, respectively. The accuracies were in the range of -24% to 16%, and recoveries ranged from 25% to 100%. The LC-MS-MS method proved to be simple and robust for the determination of drugs in hair. It has been used for authentic samples in our laboratory in the past year.

Stress-induced attenuation of acoustic startle in low-saccharin-consuming rats.

Biol Psychol. 2008 May 3;
Gonzales M, Garrett C, Chapman CD, Dess NK
Exposure to stress can lead to either increased stress vulnerability or enhanced resiliency. Laboratory rats are a key tool in the exploration of basic biobehavioral processes underlying individual differences in the effect of stress on subsequent stressors' impact. The Occidental low (LoS) and high (HiS) saccharin-consuming rats, which differ in emotional reactivity, are useful in this effort. In the present study, footshock affected acoustic startle amplitude 4h later among LoS but not HiS rats. Surprisingly, shock attenuated startle rather than sensitizing it, a finding not previously reported for male rats exposed to shock. Attenuation was blocked by administering the anxiolytic drug alprazolam prior to stress, implicating anxiety in the effect. Preliminary tests provided no evidence of mediation by adenosine or corticosterone. This novel result encourages further study of the stressor and dispositional variables that modulate the timecourse of effects of stress on startle and identification of its mechanisms.

 

This page was last reviewed by Dr Greg Mulhauser, Friday, 4 July 2008.

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