Title |
Pharmacological analysis of the increases in heart rate and diastolic blood pressure produced by (S)-isometheptene and (R)-isometheptene in pithed rats
|
---|---|
Published in |
The Journal of Headache and Pain, May 2017
|
DOI | 10.1186/s10194-017-0761-y |
Pubmed ID | |
Authors |
Alejandro Labastida-Ramírez, Eloísa Rubio-Beltrán, Oswaldo Hernández-Abreu, Bruce L. Daugherty, Antoinette MaassenVanDenBrink, Carlos M. Villalón |
Abstract |
Isometheptene is a sympathomimetic drug effective in acute migraine treatment. It is composed of two enantiomers with diverse pharmacological properties. This study investigated in pithed rats the cardiovascular effects of (S)- isometheptene and (R)-isometheptene, and the pharmacological profile of the more potent enantiomer. The effects of i.v. bolus injections (0.03, 0.1, 0.3, 1 and 3 mg/kg) of isometheptene racemate, (S)-isometheptene or (R)-isometheptene on heart rate and blood pressure were analyzed in control experiments. The enantiomer producing more pronounced tachycardic and/or vasopressor responses was further analyzed in rats receiving i.v. injections of prazosin (0.1 mg/kg), rauwolscine (0.3 mg/kg), propranolol (1 mg/kg) or intraperitoneal reserpine (5 mg/kg, -24 h). Compared to (R)-isometheptene, (S)-isometheptene produced greater vasopressor responses, whilst both compounds equipotently increased heart rate. The tachycardic responses to (S)-isometheptene were abolished after propranolol, but remained unaffected by the other antagonists. In contrast, the vasopressor responses to (S)-isometheptene were practically abolished after prazosin. Interestingly, after reserpine, the tachycardic responses to (S)-isometheptene were abolished, whereas its vasopressor responses were attenuated and subsequently abolished by prazosin. The different cardiovascular effects of the isometheptene enantiomers are probably due to differences in their mechanism of action, namely: (i) a mixed sympathomimetic action for (S)-isometheptene (a tyramine-like action and a direct stimulation of α1-adrenoceptors); and (ii) exclusively a tyramine like action for (R)-isometheptene. Thus, (R)-isometheptene may represent a superior therapeutic benefit as an antimigraine agent. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 17 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 4 | 24% |
Student > Master | 2 | 12% |
Student > Bachelor | 2 | 12% |
Other | 1 | 6% |
Lecturer | 1 | 6% |
Other | 3 | 18% |
Unknown | 4 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 2 | 12% |
Neuroscience | 2 | 12% |
Nursing and Health Professions | 2 | 12% |
Biochemistry, Genetics and Molecular Biology | 1 | 6% |
Agricultural and Biological Sciences | 1 | 6% |
Other | 5 | 29% |
Unknown | 4 | 24% |