Photodegradation products of propranolol: the structures and pharmacological studies.
Recently, single-dose drug packaging systems, allowing the administration of multiple drugs in a single pill, have become popular for the convenience of the patient. The quality of drugs and an accurate measurement of their photostabilities within this system, however, have not been carefully addressed. Drugs that are unstable in light should be carefully handled to protect their potency and ensure their safety. Propranolol (1), a beta-adrenergic receptor antagonist, is widely used for angina pectoris, arrhythmia, and hypertension. Due to its naphthalene skeleton, this drug may be both light unstable and a photosensitizing agent. In this study, we isolated three photodegraded products of propranolol (1): 1-naphthol (2), N-acetylpropranolol (3), and N-formylpropranolol (4). The structures of these compounds were determined by spectroscopic methods and chemical syntheses. We also examined the acute toxicities of these substances in mice and their binding to beta-adrenergic receptors using rat cerebellum cortex membranes. Although the photoproducts isolated in this study did not exhibit any acute toxicity or significant binding to beta-adrenergic receptors, these results serve as a warning to single-dose packaging systems, as propranolol (1) must be handled carefully to protect the compound from light-induced degradation.
Uwai
Koji
K
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, and Department of Pharmacy, Sendai Social Insurance Hospital, Sendai, Japan. uwai@tohoku-pharm.ac.jp
Tani
Marie
M
Ohtake
Yosuke
Y
Abe
Shinya
S
Maruko
Akiko
A
Chiba
Takashi
T
Hamaya
Yoshiro
Y
Ohkubo
Yasuhito
Y
Takeshita
Mitsuhiro
M
D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004355:Drug Stability; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009284:Naphthols; D010777:Photochemistry; D010782:Photolysis; D011433:Propranolol / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D014466:Ultraviolet Rays
D000319:Adrenergic beta-Antagonists; D009284:Naphthols; D011943:Receptors, Adrenergic, beta; C029350:1-naphthol; D011433:Propranolol