ACADIA Pharmaceuticals Inc.

About: ACADIA Pharmaceuticals Inc. is a company organization based out in San Diego, California, United States. It is known for research contribution in the topics: Pimavanserin & Receptor. The organization has 260 authors who have published 276 publications receiving 8418 citations.

Discriminative stimulus effects of the type-4 phosphodiesterase inhibitor rolipram in rats.

Abstract: Rationale: Rolipram, an inhibitor of cyclic AMP phosphodiesterase (PDE4) produces discriminative stimulus effects in rats. These effects may be related to a wide range of central nervous system effects described previously. Objective: The purposes of the present study were to: (i) assess the specificity of the discriminative stimulus effects of rolipram; (ii) examine the role of beta adrenergic receptors; (iii) assess the effects of imipramine and nisoxetine; and (iv) determine whether SKF 38393, a compound which also increases cAMP levels, substitutes for rolipram. Methods: Rats were trained to discriminate 0.1 mg/kg rolipram from its vehicle in a two-lever task. Following discrimination training, substitution and antagonism tests were carried out. Results: In generalization tests, the PDE4 inhibitors ICI 63,197 and Ro 20-1724 substituted for rolipram in a dose-dependent manner (substitution at 0.3 mg/kg and 3 mg/kg, respectively). The selective inhibitors of PDE1, PDE2, and PDE5/6 did not substitute for rolipram; however, a dose of 10 mg/kg of the PDE3 inhibitor milrinone did substitute. The beta adrenergic agonists clenbuterol and dobutamine at least partially substituted for rolipram (0.1 mg/kg and 18 mg/kg, respectively). By contrast, the D1 dopaminergic agonist SKF 38393 and the monoamine uptake inhibitors imipramine and nisoxetine were ineffective (at doses up to 3, 10, and 10 mg/kg, respectively). Conclusions: The present results indicate that the discriminative stimulus effects of rolipram are related to the inhibition of the hydrolytic activity of PDE4. Generalized increases in cyclic nucleotides do not appear to be sufficient for producing rolipram-like effects. It appears that a mechanism involving beta adrenergic receptors may contribute to the effects of rolipram, consistent with previous neuropharmacological data. Finally, the discriminative stimulus effects of rolipram appear to be unrelated to its antidepressant-like effect, but may provide a surrogate marker for central nervous system-related side effects of PDE4 inhibitors.

Reduction of haloperidol-induced side effects by ACP-103 in healthy volunteers

Abstract: Background/Aims A novel serotonin 2A (5-HT2A) receptor inverse agonist, ACP-103, was tested to determine the potential of ACP-103 to inhibit central nervous system side effects produced by haloperidol. Methods Healthy male volunteers participated in a randomized, double blind, placebo-controlled, single dose crossover study. All subjects received a single dose of haloperidol (7.5 mg) in combination with either a single dose of placebo or a single dose of ACP-103 (100 mg). The washout period between treatment combinations was two weeks. Results Haloperidol caused measurable akathisia in 13 of 18 subjects and induced approximately a 3-fold increase in prolactin secretion. ACP-103 treatment caused a measurable and temporally consistent decrease in haloperidol-induced akathisia compared to placebo treated subjects as measured by the Barnes Akathisia Scale. ACP-103 significantly reduced haloperidol-induced hyperprolactinemia. The pharmacokinetics of haloperidol and ACP-103 were not affected by their co-administration. No serious adverse events were reported. Conclusions Data suggest that ACP-103, when co-administered with existing antipsychotic drugs, may reduce their side effects and expand their range of efficacy. ACP-103 is being developed as an adjunctive therapy for schizophrenia and as a therapy for treatment-induced dysfunction in Parkinson's disease. Clinical Pharmacology & Therapeutics (2005) 77, P98–P98; doi: 10.1016/j.clpt.2005.01.004

A 3-way Cross-over Study of Pregabalin, Placebo, and the Histamine 3 Receptor Inverse Agonist AZD5213 in Combination With Pregabalin in Patients With Painful Diabetic Neuropathy and Good Pain-reporting Ability.

Abstract: OBJECTIVES In this study, patients with painful diabetic neuropathy were trained using an experimental pain paradigm in an attempt to enroll a subset of patients who are "pain connoisseurs" and therefore more able to discriminate between active and placebo treatments. METHODS AZD5213, a novel histamine H3 receptor inverse agonist+pregabalin, pregabalin, and placebo were then tested in a 3-period cross-over. RESULTS The study did not provide any evidence of clinical efficacy for AZD5213 when combined with pregabalin in the treatment of painful diabetic neuropathy. DISCUSSION The training of study patients in pain reporting and subsequent enrichment with good pain reporters also did not enable the robust detection of the efficacy of pregabalin relative to placebo in a small sample size. Further work is required before recommending the use of "connoisseur" patients in future neuropathic pain studies.

Experiencing Parkinson’s Disease Psychosis via Virtual Reality Simulation: A Novel and Effective Educational Tool (P1.011)

Abstract: Objective: To examine the accuracy and effectiveness of a novel virtual reality (VR) simulation tool in capturing Parkinson’s disease psychosis (PDP) Background: Despite its frequency, there remains confusion regarding diagnosing PDP. This may reflect knowledge gaps of its spectrum (i.e., illusions, hallucinations, delusions), overlapping non-motor issues (i.e., vivid dreams, dementia), failure of patients/caregivers and healthcare providers (HCP) to discuss PDP, or an inability to “see what patients see” in visual hallucinations. With VR technology, one can simulate experiences not possible in “real life,” and these simulations may provide useful educational tools. Design/methods: We developed a novel VR simulation of PDP using Oculus rift technology and descriptions by patients, caregivers, and HCP. The simulation, which included two hallucinatory scenarios, was presented at the 2015 AAN and Movement Disorder Society meetings. Viewers at the latter meeting completed an IRB-approved questionnaire, using a 5-point Likert-scale (“very unlikely” to “very likely”), to rate the simulation’s accuracy of capturing PDP symptoms and impact, effectiveness as a teaching tool, influence on medical practice, and side effects. Results: Questionnaires were completed by 502/602 (83.4[percnt]) viewers (56.8[percnt] Movement Disorder specialists, 40[percnt] Allied HCP/Other). Both VR scenarios accurately (“likely/very likely”) captured PDP symptoms reported by patients and caregivers (76.4[percnt], 67.6[percnt], respectively) and their impact on patients and caregivers (78.4[percnt], 66.2[percnt], respectively). The scenarios were “likely/very likely” to be effective teaching tools for HCP (87.5[percnt]) and caregivers (90.8[percnt]), though slightly less for patients (76.1[percnt]). About 50[percnt] of respondents would “likely/very likely” change their medical practice. Few experienced difficulties using the simulation, though mild motion sickness was occasionally reported. Conclusions: Using virtual technology, viewers were able to experience PDP first-hand. The PDP VR simulation has potential as an educational tool for not only HCP, but also caregivers and patients. Greater awareness of PDP may help reduce diagnostic confusion and associated stigma. Disclosure: Dr. Goldman has received personal compensation for activities with Acadia, Teva and Pfizer as a consultant and Advisory Board Member. Dr. Goldman has received research support from NIH, Michael J. Fox Foundation, Rush University Medical Center, Parkinson9 Dr. Stebbins has nothing to disclose. Dr. Fredericks has nothing to disclose. Dr. Upchurch has nothing to disclose.