Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0595921 (intraocular pressure)
 11,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A relatively selective agonist of kappa opioid receptors (KOR), bremazocine (BRE), lowers intraocular pressure in rabbits, in part, by increasing natriuretic peptide levels in aqueous humor and by enhancing total outflow facility (TOF). Natriuretic peptide (NP) levels [atrial NP (ANP), brain NP (BNP), and C-type NP (CNP)] were measured in aqueous humor of rabbits either by radioimmunoassay or enzyme immunoassay. TOF was determined in rabbits by two-level constant pressure perfusion of the anterior chamber. Experimental regimens included topical treatment with BRE in the presence or absence of KOR antagonist (norbinaltorphimine), protein kinase C inhibitor (chelerythrine), and natriuretic peptide receptor antagonist (isatin). The rank order of basal NP levels in aqueous humor of rabbits was BNP CNP > ANP. Topical administration of BRE (1-100 microg) caused dose-related elevations of CNP levels in aqueous humor that were inhibited by topical pretreatment with either norbinaltorphimine (100 microg, bilaterally) or chelerythrine (10 microg, bilaterally). Topically administered BRE (100 microg) also elevated levels of ANP and BNP in aqueous humor and evoked an 80% increase in TOF. The increase in TOF was antagonized by topical pretreatment with either norbinaltorphimine (100 microg, bilaterally) or isatin (100 microg, bilaterally). Bremazocine induced an increase in NP (ANP, BNP, and CNP) levels and TOF in rabbits by activating KOR. The increase in CNP levels elicited by BRE was inhibited by norbinaltorphimine and chelerythrine; therefore, this event is most likely mediated by a KOR-linked activation of protein kinase C. These data provide evidence that the increase in TOF elicited by BRE was mediated by a KOR-activated paracrine effect of NPs on tissues within ocular outflow tract(s).
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PMID:Bremazocine increases C-type natriuretic peptide levels in aqueous humor and enhances outflow facility. 1474 37

Bremazocine is a kappa-opioid receptor agonist with potent analgesic and diuretic activities. As an analgesic it is three- to four-times more potent than morphine, as determined in both hot plate and tail flick tests. Bremazocine and other benzomorphan analogs were synthesized in an effort to produce opiates with greater kappa-opioid receptor selectivity and with minimal morphine-like side effects. Unlike morphine bremazocine is devoid of physical and psychological dependence liability in animal models and produces little or no respiratory depression. While bremazocine does not produce the characteristic euphoria associated with morphine and its abuse, it has been shown to induce dysphoria, a property that limits its clinical usefulness. Similarly to morphine, repeated administration of bremazocine leads to tolerance to its analgesic effect. It has been demonstrated that the marked diuretic effect of bremazocine is mediated primarily by the central nervous system. Because of its psychotomimetic side effects (disturbance in the perception of space and time, abnormal visual experience, disturbance in body image perception, de-personalization, de-realization and loss of self control) bremazocine has limited potential as a clinical analgesic. However, its possible utility for the therapy of alcohol and drug addiction warrants further consideration because of its ability to decrease ethanol and cocaine self-administration in non-human primates. In addition, the ability of bremazocine-like drugs to lower intraocular pressure and to minimize ischemic damage in animal models suggests their possible use in the therapy of glaucoma and cardiovascular disease.
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PMID:Bremazocine: a kappa-opioid agonist with potent analgesic and other pharmacologic properties. 1600 40