medical image

Models & Techniques

bottom shadow

7% CO2 model to evoke anxiety symptoms in healthy subjects

.

Conceiving and validating anxiety models in healthy subjects (HV) and patients was needed for cost- and time effective drug development to support novel chemical entities characterised in preclinical models of anxiety.

Some substances or conditions as inhalation of CO2 are panicogen in man and can reproduce in healthy subjects core symptoms of panic attack similar to those reported in Panic Disorder patients.

A model was developed by generating anxiety symptoms in HV through the administration of 7% CO2 for 20min. HV were given in balanced order 7% CO2 or compressed air as control condition in two separate sessions and this challenge, in comparison with compressed air, produces measurable response (Panic Symptom list (PSLIII-R), Visual scale (VAS-A), STAI Anxiety Inventory (STAI-Y/1), respiratory parameters and skin conductance) in susceptible subjects.

The model was validated by applying this challenge before and after the administration of alprazolam, a drug known to reduce anxiety symptoms, which resulted to be able to reduce subjective and objective symptoms.

In conclusion, evoking anxiety symptoms by a 7% CO2 challenge with good test-retest repeatability in healthy subjects is a reliable model to test potential anxiolytic effects of a new chemical compound.

See the publications about this model:

  • Alprazolam and the neurokinin-1 receptor antagonist GW 597599 ...
  • Changes in neuroactive steroid secretion associated with CO2 ...
  • Characterization of a 7% carbon dioxide (co2) inhalation paradigm ...

Ejaculation Latency Test as a tool to evaluate drugs with efficacy in Premature Ejaculation disorder.

Premature Ejaculation (PE) is one of the most common forms of male sexual dysfunction in men younger than 40 years, affecting from 20% to 30% of men.

Serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and delayed ejaculation, while their effect on other aspects of sexual function, such as sexual motivation, arousal, and erectile function are unclear.

In an attempt to translate a previous preclinical study performed in rat, the Ejaculation Latency Test was used as a tool to evaluate sexual function in patient with PE disorder evaluating the effect of chronic administration of an SSRI, on normal sexual functions.

The test administrated at screening and at the end of the study treatment records the masturbation ejaculation latency time (MELT) performed during visual erotic stimulation, and uses self-filled questionnaires (International Index Erectile Function [IIEF-15] and Golombock Rust Inventory of Sexual Satisfaction [GRISS]).

See the publications about this model

  • The effects of citalopram and fluoxetine on sexual behavior ...
  • A double blind, parallel group, placebo controlled study ...
  • Messa a punto di un modello sperimentale per valutare il tempo di eiaculazione ...

Dental Impaction Pain Model as a tool to evaluate drugs with efficacy in Inflammatory and Neuropathic Pain.

The dental pain model of tooth extraction is a recognized and validated tool for assessment of clinical efficacy of drugs for inflammatory pain.

Patients already scheduled for 3rd molar tooth extraction, who were otherwise healthy, were recruited for this study.

After completion of tooth extraction patients were asked to rate the intensity of their pain. As soon this rate reached a medium intensity, patients were randomized and dosed with the study medication.

Patients were therefore asked to abstain from any other analgesic medication use for at least 1 hrs post dosing (this time is considered acceptable also for patients receiving placebo treatment), unless the pain become intolerable. Then, if the patient reported the persistence of his pain, a rescue medication was given.

A battery of rating scales was used to evaluate the self perceived intensity of pain before and after treatment. Usually a Visual Analogue Scale and a Verbal Rating Scale are used for this purpose.

See the publications about this model

  • White Paper - Analgesic Agents and Strategies in Pain Research
  • Dexketoprofen/tramadol: randomised double-blind trial ...
  • A Randomized, Controlled Study to Investigate the Analgesic Efficacy ...
  • Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination ...

Topical Capsaicin Cream as a tool to evaluate drugs with efficacy in Neuropathic Pain.

The receptor for capsaicin, designated vanilloid receptor subtype 1 (VR1) works as a general sensor of noxious stimuli and id expressed in both the peripheral and central nervous system within centers known for their role in pain detection, transmission and regulation.

Capsaicin cream was administered to the skin of the volar forearm during each study visit, at a site approximately 10 to 15 cm from the wrist and left for 30 minutes.

Quantitative sensory testing with a Neuro-Sensory Analyzer was allowed for registering the heat perception threshold and the heat pain perception before and after the capsaicin administration.

The Heat Perception Threshold (HPT) and the Pain Perception Threshold (HPPT) was measured using the Medoc TSA-II Neurosensory Analyser, a computer-controlled device capable of generating highly repeatable thermal stimuli and recording the time of the response given from the volunteers.

Measurements were performed before capsaicin administration and then after its removal for the following 30 minutes (at 5 minute-interval).

Secondary measurements included intensity of the flare reaction of the skin, self perceived reporting of pain intensity and extension of the allodinia area by using the Von Frey Hair Test.


Computerised Tests (attention and memory)

  • Simple Reaction Time test (e-prime module)
  • Sternberg Memory test (e-prime module)
  • Digit Span Test (e-prime module)
  • Stroop Test (e-prime module)

Tracking-Attention

  • Wechsler Adult Intelligence Scale-Revised
    • Digit Symbol Substitution Test (DSST)
  • The ‘Deux Barrages’ Test (DBT)

Mood

  • Positive and Negative Affect Schedule (PANAS)
  • The Profile of Mood States (POMS)
  • The Bond & Lader Visual Analogue Scale of Mood and Alertness (BLVAS)

Memory

  • The Hopkins Verbal Learning Test - Revised (HVLT-R)
  • Working Memory: (Sequential Number Recall Task)


Sleep

  • The Pittsburgh Sleep Questionnaire (PSQI)
  • The Leeds Sleep Evaluation Questionnaire (LSEQ)
  • The Stanford Sleepiness Scale (SSS)

Smoking Dependence

  • The Fagerström Tolerance Questionnaire
  • Shiffman Smoking Questionnaire *
  • Schneider Smoking Questionnaire *
  • Questionnaire on Smoking Urge - Brief Form

A 72 hour humane model to assess Craving and Withdrawal symptoms and signs.

A smoking human model was developed to assess possible efficacy of new drugs developed for smoking cessation where a rat model of nicotine relapse was preclinically used. In a double blind, randomised, 3-period, crossover study, smoker healthy volunteers went through three periods of: free smoking, enforced abstinence with study drug and enforced abstinence with placebo.

Each period consisted of 3 days (72 hours) of observation. Subjects that receive active treatment or placebo quit smoking abruptly at 7:30 am of day 1 of observation (about 8 hours after the first dose administration).

Active and placebo treatment administration were administered every 24 hours on day 1, 2 and 3. Craving (QSU-Brief), Mood (PANAS), Withdrawal Symptoms (SCS) questionnaires and HR blood pressure, skin conductance Breath Carbon Monoxide (CO) and Saliva Cotinine were recorded at several time points.

See the publications about this model

  • Effect of bupropion sustained-release (SR) on craving ...
  • Smokers deprived of cigarettes for 72h ...
  • Correlation and predictive performances of saliva and plasma ...
  • Verifica della validità esteriore e del contenuto della versione italiana di tre questionari su craving ...
  • Cues impact on craving and mood, during 3-day periods ...
  • Cigarette smoking abstinence: mood, anxiety ...
  • Gabab receptor agonist (baclofen): effects on smoking ...
  • Craving and withdrawal symptoms during acute smoking absistance ...
  • Fagerström tolerance questionnaire, time to first cigarette ...
  • Different Patterns of Craving and Withdrawal Symptoms ...
  • Smoker complaint scale (scs): factorial structure ...
  • Correlation and predictive performances of saliva and plasma nicotine concentration on tobacco ...
  • Craving and withdrawal symptoms in a short term period (72 hours) ...
  • Cigarette Smoke Craving and Withdrawal Symptoms ...
  • Inflammatory cells and mediators in induced sputum of young healthy smokers and ...

EEG With Acoustic, Visual, Sensorial And Motor Evoked Potential.

See the publications about this model

  • EEG power spectra and auditory P300 during free smoking ...
  • Effects of a small dose of triazolam on cognitive function ...
  • Evaluation of resting EEG and auditory P300-EPs ...

An Applicable Model In Humans With New Drug In Early Phase Clinical Trials.

Recently we performed an experimental clinical trial with alprazolam using fMRI in resting state as a radiological tool.

The aim of the study was to highlight the presence of modifications in the Default Mode Network (DMN) detected by means of fMRI in Resting State after the administration of a neurotropic drug, the Alprazolam, and therefore to suggest fMRI as an alternative and non invasive tool for future pharmacological experimentations in vivo.

The reproducibility of fMRI in Resting State was demonstrated with a consistent detection of DMN in all subjects and all conditions, furthermore a statistically non-significant difference between baselines was found.

The Dual-Regression analysis showed a diffuse significant higher functional connectivity in the brain after the administration of Alprazolam, mainly in the precuneus/posterior cingulate cortex within the DMN, and also between the DMN and other cerebral areas, in particular the basal ganglia.

No significant differences in DMN were detected after placebo administration. Hence, fMRI should be considered an applicable model in humans with new drug in early phase clinical trials.

See the publications about this model

  • fMRI in resting state as a radiological tool in pharmaceutics research ...

Pulmonary Function Testing With Provocation Challenges And Induced Sputum Test

Magnetic Trans-Cranial Stimulation

Ultrasonographic Gastric Emptying Test