Cerebral Pharmacodynamic Effects of 5-HT1B Receptor Stimulation

Cerebral Pharmacodynamic Effects of 5-HT1B Receptor Stimulation

The purpose of this study is to show that PET-MR imaging can be used for obtaining a pharmacodynamic profile of drugs. By using the 5-HT1B receptor as target we also aim to find effect areas and sizes of the 5-HT1B receptor agonist sumatriptan.

Recent technological advances in multimodal imaging have enabled the simultaneous acquisition of magnetic resonance imaging (MRI) and PET data. Whereas functional MRI (fMRI) provides excellent spatio-temporal resolution for localizing changes in brain activity, PET offers high sensitivity and neurochemical specificity. Together, PET and MRI measures have the potential to help clarify the neurochemical basis of changes in fMRI signal induced by selective exogenous ligands or endogenous neurotransmitter.

In the present study we will target the 5-HT1B receptor for which a selective radioligand exist (11C-AZ10419369). The receptor can be stimulated with the agonist sumatriptan, which is used for alleviating migraine attacks. The mechanism of action of sumatriptan is not precisely known and it is unknown to what degree sumatriptan crosses the blood-brain barrier and exerts its effect in the parenchyma. In this study we can determine the blood brain barrier penetration of sumatriptan and thereby evaluate Effect sizes, distribution of signal changes, and correlation between the occupancy at the 5-HT1B receptor in the parenchyma (measured by changes in BPND) and the hemodynamic response (measured by changes in CBF).

Ahead of the main study a pilot study will be conducted in which increasing doses of sumatriptan will be tested in the same subject to obtain a dose-response curve. At the same time side effects will be observed and scored. This serves to find the dose with maximum effect size but minimal side effects, which can then be used in the main study for all subjects.

Inclusion Criteria:

• Healthy subjects
• Age 18-60

Exclusion Criteria:

• Primary psychiatric disease (DSM IV Axis I or WHO ICD-10 diagnostic classification).
• Present or former neurological diseases,
• Severe somatic disease
• Medication that can interfere with the test results.
• Doesn't speak Danish fluently or is severely, visually or hearing impaired.
• Information regarding former learning disabilities.
• Pregnancy at the time of the scanning
• Breast feeding
• MR-scanner incompatibility (metal in soft tissue)
• Alcohol or drug abuse
• Allergy to ingredients in used drugs
• Participation in experiments with radioactivity (>10 mSv) within the last year or considerable work-related exposure to radioactivity.