Related Experiment Video
Updated: Jun 27, 2026

3D-Neuronavigation In Vivo Through a Patient's Brain During a Spontaneous Migraine Headache
Published on: June 2, 2014
Preclinical studies characterizing the anti-migraine and cardiovascular effects of the selective 5-HT1D receptor
1Department of Neurobiology and Structural, Analytical and Medicinal Chemistry, Pharmacia Corporation, Kalamazoo, MI 49001, USA. robert.b.mcall@pharmacia.com
Abstract:
The present study describes the preclinical pharmacology of a highly selective 5-HT1D receptor agonist PNU-142633. PNU-142633 binds with a Ki of 6 nm at the human 5-HT1D receptor and a Ki of> 18 000 nm at the human 5-HT1B receptor. The intrinsic activity of PNU-142633 at the human 5-HT1D receptor was determined to be 70% that of 5-HT in a cytosensor cell-based assay compared with 84% for that of sumatriptan. PNU-142633 was equally effective as sumatriptan and a half-log more potent than sumatriptan in preventing plasma protein extravasation induced by electrical stimulation of the trigeminal ganglion. Like sumatriptan, PNU-142633 reduced the increase in cat nucleus trigeminal caudalis blood flow elicited by electrical stimulation of the trigeminal ganglion compared with the vehicle control. The direct vasoconstrictor potential of PNU-142633 was evaluated in vascular beds. Sumatriptan increased vascular resistance in carotid, meningeal and coronary arteries while PNU-142633 failed to alter resistance in these vascular beds. These data are discussed in relation to the clinical findings of PNU-142633 in a phase II acute migraine study.
Related Concept Videos
Direct-Acting Cholinergic Agonists: Pharmacological Actions
Cholinergic Antagonists: Pharmacological Actions
Gastrointestinal Effects: Antimuscarinics reduce gut contractions, increase gastric emptying, and slow intestinal transit. They partly inhibit gastric acid secretion...
Cholinergic Antagonists: Therapeutic Uses
Respiratory Tract: Ipratropium, aclidinium, and tiotropium treat asthma, chronic bronchitis, and chronic obstructive pulmonary disease (COPD). They protect against bronchoconstriction caused by irritants like cigarette smoke, sulfur dioxide, and ozone. They also help reduce nasopharyngeal secretions in common...
Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

