Abstract
This study was designed to determine if the histamine H3 receptor agonist R-alpha-methylhistamine would play a role in modulation of sympathetically evoked mydriasis in anesthetized rats, and if so, to ascertain the specific receptor subtype(s) involved. Reproducible frequency-response curves of pupillary dilation were generated by stimulation of the cervical preganglionic sympathetic nerve (1-32 Hz). Systemic administration of R-alpha-methylhistamine (0.3-3.0 mg kg(-1)) produced a dose-related inhibition of the evoked mydriasis. The greatest inhibition was seen at lower frequency levels, with about 43% depression observed at 2 Hz. The specific histamine H3 receptor antagonist, clobenpropit (3.0 mg kg(-1), i.v.), blocked the inhibitory effect of R-alpha-methylhistamine, whereas neither the histamine H2 receptor antagonist, cimetidine (5.0 mg kg(-1), i.v.), nor the histamine H1 receptor antagonist, chlorpheniramine (0.5 mg kg(-1), i.v.), was effective. The histamine H2 receptor agonist, dimaprit (10 mg kg(-1), i.v.), was also without effect on the evoked mydriasis. R-alpha-methylhistamine (3.0 mg kg(-1)) did not inhibit phenylephrine-induced mydriasis. These results support the conclusion that R-alpha-methylhistamine produces inhibition of sympathetically evoked mydriasis via histamine H3 receptor stimulation, presumably by an action on presynaptic histamine H3 receptors.
| Original language | English |
|---|---|
| Pages (from-to) | 55-9 |
| Number of pages | 5 |
| Journal | European Journal of Pharmacology |
| Volume | 419 |
| Issue number | 1 |
| Publication status | Published - 04 May 2001 |
Keywords
- Animals
- Chlorpheniramine
- Cimetidine
- Dimaprit
- Dose-Response Relationship, Drug
- Electric Stimulation
- Histamine Agonists
- Histamine Antagonists
- Histamine H1 Antagonists
- Histamine H2 Antagonists
- Imidazoles
- Male
- Methylhistamines
- Mydriasis
- Pupil
- Rats
- Rats, Sprague-Dawley
- Sympathetic Nervous System
- Thiourea