Davis J N, Maury W
J Pharmacol Exp Ther. 1978 Nov;207(2):425-30.
Alpha adrenergic stimulation elicits a rapid release of K+ from dispersed rat parotid cells. Surprisingly neither clonidine, oxymetazoline, naphazoline, ST 600 nor ST 91 elicited K+ release from parotid cells at concentrations up to 100 micrometer. By contrast, these agents were able to block epinephrine-stimulated K+ release with the relative potencies: oxymetazoline more than naphazoline more than clonidine more than ST 600 more than ST 91. [3H]-Dihydroergocryptine (DHE) binds to sites on parotid membranes and intact dispersed cells with the characteristics of alpha adrenergic membrane receptors. The ability of these imidazolines to displace [3H]DHE binding from parotid membranes correlated with their potencies as alpha adrenergic antagonists in the dispersed cells. Although clonidine, oxymetazolin and naphazoline are agonists in other peripheral alpha adrenergic receptors, they are antagonists in the parotid. This observation explains the most common side-effect of clonidine administration, dry mouth, and is consistent with the proposition that different groups of alpha adrenergic receptors exist in mammalian tissues. These data also suggest that the central actions of clonidine must be interpreted with caution since alpha adrenergic receptors similar to those in the parotid may be present in brain.
α肾上腺素能刺激可促使大鼠腮腺分散细胞快速释放钾离子。令人惊讶的是，可乐定、羟甲唑啉、萘甲唑啉、ST 600和ST 91在浓度高达100微摩尔时均未引发腮腺细胞释放钾离子。相比之下，这些药物能够以相对效力阻断肾上腺素刺激的钾离子释放：羟甲唑啉＞萘甲唑啉＞可乐定＞ST 600＞ST 91。[3H] - 二氢麦角隐亭（DHE）以α肾上腺素能膜受体的特性与腮腺膜及完整分散细胞上的位点结合。这些咪唑啉类药物从腮腺膜上取代[3H]DHE结合的能力与其作为分散细胞中α肾上腺素能拮抗剂的效力相关。尽管可乐定、羟甲唑啉和萘甲唑啉在其他外周α肾上腺素能受体中是激动剂，但在腮腺中却是拮抗剂。这一观察结果解释了可乐定给药最常见的副作用——口干，并且与哺乳动物组织中存在不同组别的α肾上腺素能受体这一观点一致。这些数据还表明，由于大脑中可能存在与腮腺中类似的α肾上腺素能受体，因此对可乐定的中枢作用必须谨慎解读。
