Ampakines

Authors:

Alexander L Miller, Andrew C Leon, Donald C Goff, Jayendra Patel, Michael F Green, Oliver Freudenreich, Steven A Johnson, Steven Lamberti, Theo Manschreck

Findings:

Subjects were assessed with a cognitive battery. (Findings not detailed in the provided snippet).

Participants:

Stable schizophrenia patients treated with clozapine (n=52), olanzapine (n=40), or risperidone (n=13)

Dosage:

CX516 900 mg three times daily

Study Quality Assessment:

Randomly assigned to add-on treatment with CX516 or placebo for 4 weeks. Sample sizes for subgroups: clozapine (n=52), olanzapine (n=40), risperidone (n=13).

Findings:

Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. It tended to decrease switching errors in the CTMT. Drug-induced side effects included headache, somnolence, and nausea, with subjects experiencing SEs having higher plasma levels of farampator and worse memory performance compared to those without SEs in the farampator condition.

Participants:

16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years)

Dosage:

500 mg farampator (single dose)

Study Quality Assessment:

Double-blind, placebo-controlled, randomized, cross-over study. N=16. Testing 1 h after drug intake (around Tmax). Tasks assessed episodic memory (wordlist learning, picture memory), working/short-term memory (N-back, symbol recall), motor learning (maze task, pursuit rotor), and information processing (tangled lines task, SDST, CTMT). Side effects reported.

All Effects:

Findings:

AMPA receptors play an important role in biological consequences following spinal cord injury (SCI), including breathing, pain, inflammation, bladder control, and motor function. In animal models, AMPAR antagonists generally show protective effects early after injury, while potentiators (ampakines) can improve breathing and bladder function. The timing of AMPAR modulation post-injury is critical, and the paper strongly encourages further studies on AMPARs as therapeutic targets for SCI.

Participants:

Animal models of SCI. The text states no clinical trial data has been reported in human SCI patients to date.

Study Quality Assessment:

Based on preclinical models (animal models of SCI). The paper summarizes and discusses existing data to document proof of principle. No clinical trial data in human SCI patients is reported. A conflict of interest is declared: some authors (AL, JMW, and RC) are associated with RespireRx Pharmaceuticals Inc., which owns the AMPA receptor potentiators CX1739 and CX717 discussed in the paper.

All Effects:

Findings:

Ampakines, drugs derived from aniracetam, potentiate AMPA receptor currents, enhance synaptic responses, and long-term potentiation. Type I (e.g., CX546) prolong synaptic responses and enhance long-term depression, while Type II (e.g., CX516) mainly increase response amplitude; they act via separate sites. Ampakines facilitate learning, improve short-term memory in various paradigms, correct behaviors in animal models of schizophrenia/depression, show positive results in human psychological tests, have few adverse effects at therapeutic concentrations, and are neuroprotective, partly by mobilizing BDNF; Type II drugs like CX516 appear inherently safe.

Participants:

Animal models of schizophrenia and depression; human subjects (for psychological tests).

Dosage:

therapeutically relevant concentrations (specific values not provided)

Study Quality Assessment:

This text describes a review focusing on physiological studies. It mentions methods like 'binding assays' and 'behavioral tests'.

All Effects: