Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apomorphine produced a greater hypothermic response in spontaneously hypertensive rats (SHRs) than in normotensive Wistar-Kyoto rats (WKYs). Experiments were conducted in SHRs and WKYs of three age groups to determine whether the increased hypothermic responsiveness to apomorphine occurs prior to the development of hypertension. The mean systolic blood pressures (SBPs) of SHRs and WKYs were comparable at 4-6 weeks of age. The mean SBP of SHRs were significantly greater than that of WKYs at both 8-10 and 12-15 weeks of age. Yet SHRs responded to apomorphine with significantly greater hypothermia than WKYs at all three ages. These findings indicate that the hyperresponsiveness of SHRs to apomorphine-induced hypothermia precedes the development of hypertension. This sequence of events is consistent with the hypothesis that central DA systems play a role in development of hypertension in SHRs.
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PMID:Increased apomorphine-induced hypothermia precedes development of hypertension in SHRs. 178 66

Brain catecholamines may play a role in the development of hypertension in the spontaneously hypertensive rat (SHR). To investigate central dopaminergic function in this strain, the effect of various dopaminergic drugs on open-field activity was assessed. In general, basal levels of ambulation were similar in SHRs and their controls, the Wistar-Kyoto rats (WKY). Exploratory rearing activity was increased in SHRs, however. Haloperidol inhibited open-field ambulation in SHRs and WKY, but higher doses were needed in the SHR. Apomorphine inhibited ambulatory activity in WKY but had virtually no effect in SHRs. Amphetamine and the dopamine uptake inhibitor GBR-12909 increased ambulation in SHRs and WKY to a similar extent. Central administration of haloperidol or sulpiride decreased ambulatory activity in WKY, but had no effect in SHRs at the doses used. SCH-23390 decreased ambulation scores both in SHRs and WKY, with the effect being slightly greater in the latter strain. In all cases exploratory rearing was affected as well by the drugs used. The large difference in base-line scores has to be taken into account when interpreting these data, however. Also, for comparison the noradrenergic drugs clonidine and desipramine were tested. Both elicited decreases in activity which were identical in SHRs and WKY. These results show that a number of dopaminergic drugs have differential effects on open-field activity of SHRs as compared to WKY. Ambulatory activity appeared more resistant to inhibition in SHRs than in WKY. The possibility that these results could reflect altered dopaminergic function in SHR involved in the development of hypertension in this strain is discussed.
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PMID:Differential effects of dopaminergic drugs on open-field behavior of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. 256 90

Nicotine evokes the release of catecholamines from bovine adrenal glands perfused with oxygenated Krebs-bicarbonate solution. Two 2-min pulses of 5 microM nicotine, at 40-min intervals (S1 and S2), gave net catecholamine outputs of 45.2 +/- 3.6 and 29.1 +/- 3.5 micrograms/8 min, respectively. Apomorphine (1 or 10 microM) markedly inhibited catecholamine release during S2 to 9.1 +/- 2.2 and 0.5 micrograms/8 min, respectively. Haloperidol (0.5 microM) reversed the inhibitory effects of apomorphine. Haloperidol alone enhanced catecholamine release induced by nicotine to 67.9 +/- 7.9 micrograms/8 min. [3H]Spiperone binds to adrenomedullary membranes with a KD of 0.24 nM and a Bmax of 117 fmol/mg of protein. Whereas spiperone and haloperidol potently displaced such binding, 3,4-dihydroxyphenylethylamine (dopamine) and sulpiride were poorer displacers, and SCH23390, prazosin, phenoxybenzamine, propranolol, BAY-K-8644, and nitrendipine did not displace [3H]spiperone bound. These data strongly suggest that, as in the cat, the bovine adrenal medulla chromaffin cell contains a dopaminergic receptor that modulates the catecholamine secretory process triggered by stimulation of the nicotinic cholinoceptor. Such a receptor seems to be of the D2 type and might be involved in a sympatho-adrenal cooperative mechanism contributing to the maintenance of cardiovascular homeostasis during stressful situations as well as to the pathogenesis of hypertension. If so, selective dopaminergic agonists might prove clinically useful in the treatment of hypertension.
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PMID:Characterization of a dopaminergic receptor that modulates adrenomedullary catecholamine release. 373 85

Apomorphine SL (TAP Holdings, Deerfield, IL) is a centrally acting treatment for erectile dysfunction (ED) that has been undergoing phase III trials. Over 3000 men have received apomorphine SL and over 75,000 doses have been taken. In the first three phase III parallel arm cross-over double-blind studies 854 patients were given a total of 8263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 y old and outcome measures included per attempt rates of intercourse and erections firm enough for intercourse as well as psychometric instruments and partner responses. The majority (74.1%) had moderate and severe grades of ED on admission to the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia and 16% had diabetes. Erections occurred rapidly (10-25 min) and in 54.4% of attempts at 4 mg (vs 33.8% placebo). A majority of the attempts at intercourse (50.6%) were successful at 4 mg in patients when recorded on a per-attempt basis. The most common but infrequent and mild side effect of nausea decreases with use. The phase III trials of apomorphine SL show that there is a clinically important restoration of erectile function from this new formulation of apomorphine. It has a rapid and safe effect through action in the central nervous system. Apomorphine SL brings a new choice to the management of ED that will further benefit the millions of couples affected. International Journal of Impotence Research (2000) 12, Suppl 4, S67-S73.
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PMID:Apomorphine: an update of clinical trial results. 1103 90

The central nervous system has the capacity to enhance the activity of dysfunctional penile tissue in men with erectile dysfunction (ED). Phase III clinical trials have been conducted using Apomorphine SL (TAP Pharmaceuticals, Deerfield, IL) as a centrally acting treatment for ED. Apomorphine SL has been administered to over 3,000 men in over 75,000 doses. In three phase III crossover double blind studies 854 patients were given a total of 8,263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 years old and had multiple co-morbid conditions. Outcome measures included intercourse rates and erection rates on a per attempt basis as well as psychometric instruments and partner response evaluations. The results show that 74.1% of patients had moderate or severe grades of ED on inclusion into the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia, and 16% had diabetes. Erections occurred rapidly (10-25 min). In 54.4% of attempts at 4 mg (vs 33.8% placebo, P < 0.001) erections suitable for intercourse were documented. A majority of the attempts at intercourse (50.6%, P < 0.001) were successful at 4 mg a doubling of baseline rates. Mild nausea was the most common but infrequent side effect and the rare occurrence of syncope was the most significant. No cardiac deaths were attributed. It is concluded that the clinical trials of apomorphine SL demonstrate a safe and significant rate of restoration of erectile function by means of a central mode of action. Efficacy has been shown in men with cardiovascular disease and severe grades of ED.
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PMID:Key issues from the clinical trials of apomorphine SL. 1128 67

The clinical profile for apomorphine sublingual (SL), a new centrally active agent for the management of the erectile dysfunction (ED) patient, is described in this article. Apomorphine SL is shown to be rapid in onset (71% of patients within 20 min) with a consistent, predictable response that is independent of severity (mild, moderate or severe), the underlying aetiology or the presence of significant co-morbidities (coronary artery disease, hypertension, etc). Importantly, there is also consistent long-term clinical benefit (>90% of attempts being successful over 18 months), for patients who respond to therapy and a benign side effect profile (<13.4% patients with adverse events). This formulation of apomorphine has a speed of onset and overall clinical profile that may offer particular advantages to the patient in terms of spontaneity and predictability of response. ED is a complex disease of varying aetiologies and severities often associated with a number of co-morbidities that require diverse solutions. Given the need for customisation of therapy to individual patient needs, the clinical profile of apomorphine SL would indicate that it will make a most welcome addition to the physician's armamentarium against ED.
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PMID:Characterising the benefit of apomorphine SL (Uprima) as an optimised treatment for representative populations with erectile dysfunction. 1147 90