Campbell W R, Potter D E
Department of Biology, Morris Brown College, Atlanta, Georgia 30314-4140, USA.
Ann N Y Acad Sci. 1995 Jul 12;763:463-85. doi: 10.1111/j.1749-6632.1995.tb32436.x.
These experiments sought to: (1) determine if alpha 2/I1 agonists that are topically active on the eye have similar effects on intraocular pressure when applied to the CNS and (2) ascertain whether these agents lower IOP, in part, via central alpha 2 receptors and/or imidazoline (I1) receptors. New Zealand White rabbits were fitted with chronic indwelling stainless-steel guide cannulas in several brain regions including the lateral ventricle, third ventricle (3V), or medullary intermediate reticular zone. Animals were allowed 5 days' recovery time prior to experiments measuring the effects of drugs on IOP via applanation pneumatonometry. Some animals were also pretreated with 400 micrograms of 6-hydroxydopamine injected into the lateral ventricle to determine the site of action of these alpha 2/I1 agonists. In initial experiments involving microinjection into the lateral ventricle, UK-14,304-18 evoked ocular hypotension that was inhibited by the alpha 2-antagonist rauwolscine but not by the I1-receptor antagonist efaroxan. Conversely, moxonidine and oxymetazoline were preferentially inhibited by efaroxan rather than by rauwolscine. Subsequently, experiments have shown that moxonidine and oxymetazoline, but not UK-14,304-18 will lower intraocular pressure when microinjected into the medullary intermediate reticular zone region and that efaroxan, but not rauwolscine, will inhibit ocular hypotension induced by moxonidine and oxymetazoline. Pretreatment with 6-hydroxydopamine (48 hours) completely eliminated the ocular hypotension induced by moxonidine. These preliminary data demonstrate that alpha 2- and I1-receptors in the brain mediate ocular hypotension induced by UK-14,304-18 and moxonidine/oxymetazoline, respectively. Moreover, the medullary intermediate reticular zone area of the brain stem is the probable presynaptic site mediating ocular hypotension induced by moxonidine and oxymetazoline.
（1）确定眼部局部活性的α2/I1激动剂应用于中枢神经系统时对眼压是否有类似影响；（2）确定这些药物是否部分通过中枢α2受体和/或咪唑啉（I1）受体降低眼压。给新西兰白兔在包括侧脑室、第三脑室（3V）或延髓中间网状区等几个脑区植入慢性留置不锈钢引导套管。在通过压平眼压计测量药物对眼压影响的实验前，让动物有5天的恢复时间。一些动物还预先经侧脑室注射400微克6-羟基多巴胺，以确定这些α2/I1激动剂的作用部位。在最初涉及向侧脑室微量注射的实验中，UK-14,304-18引起眼压降低，这种降低被α2拮抗剂萝芙木碱抑制，但未被I1受体拮抗剂依酚氯铵抑制。相反，莫索尼定和氧甲唑啉优先被依酚氯铵抑制，而非萝芙木碱。随后的实验表明，将莫索尼定和氧甲唑啉而非UK-14,304-18微量注射到延髓中间网状区时会降低眼压，且依酚氯铵而非萝芙木碱会抑制莫索尼定和氧甲唑啉诱导的眼压降低。用6-羟基多巴胺预处理（48小时）可完全消除莫索尼定诱导的眼压降低。这些初步数据表明，脑中的α2和I1受体分别介导UK-14,304-18和莫索尼定/氧甲唑啉诱导的眼压降低。此外，脑干的延髓中间网状区可能是介导莫索尼定和氧甲唑啉诱导的眼压降低的突触前部位。
