Pharmacological actions of AH-9700 on micturition reflex in anesthetized rats
| Autor: | Hitoshi Kohayakawa, Makoto Oka, Daisuke Ishii, Katsuyoshi Kawashima, Isao Shimizu, Seiko Oku |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Pentazocine medicine.medical_specialty Narcotic Antagonists Urinary Bladder Sigma receptor Urination Naphthalenes Pertussis toxin Cholinergic Antagonists Fumarates Internal medicine Reflex Muscarinic acetylcholine receptor medicine Animals Humans Receptors sigma Anesthesia Rats Wistar Receptor Oxybutynin Pharmacology Dose-Response Relationship Drug Chemistry Rats Endocrinology Mechanism of action Mandelic Acids Female medicine.symptom Muscle Contraction medicine.drug Muscle contraction |
| Zdroj: | European Journal of Pharmacology. 412:171-179 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/s0014-2999(00)00937-7 |
| Popis: | In radioligand binding assays, AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl]pyrrolidine fumarate) had high affinity for sigma receptors and moderate affinity for muscarinic receptors. The affinity of AH-9700 for sigma(1) receptors was significantly reduced in the presence of 5'-guanylyl-imidodiphosphate (GppNHp). In isolated bladder strips of rats, AH-9700 inhibited carbachol-induced contractions. In anesthetized rats, i.v. administration of AH-9700 and typical sigma receptor ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), but not oxybutynin, dose-dependently inhibited rhythmic isovolumetric reflex bladder contractions. AH-9700 and oxybutynin suppressed the amplitude of rhythmic bladder contractions. On the other hand, at doses lower than used i.v., the i.c.v. administration of AH-9700 or the sigma receptor ligands inhibited rhythmic bladder contractions without suppressing the amplitude. This inhibitory effect of AH-9700 was markedly reduced by pretreatment with i.c.v. pertussis toxin. These results suggest that AH-9700 exerts a marked anti-micturition reflex effect through central sigma receptors possibly related to pertussis toxin-sensitive Gi/o-proteins and a moderate spasmolytic effect based on its peripheral anti-muscarinic activity. |
| Databáze: | OpenAIRE |
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