Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (125I-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha 2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha 2, histamine H3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha 2, histamine H3 and somatostatin receptors to treatment of vascular headaches is suggested.
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PMID:UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms. 128 76

Two acromegalic patients with severe headache, persisting after pituitary adenomectomy followed by radiotherapy in one, were treated with the somatostatin analogue SMS 201-995. Both had been resistant to conventional headache therapy and experienced dramatic and rapid relief after the first injection of the analogue. This result persisted with long-term treatment of the drug. Although the mechanism of action of SMS 201-995 in pain remains unclear, the rapid and efficacious analgesic effect of this compound may be one more indication for its use in pituitary tumors associated with cephalalgias.
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PMID:Headache in acromegaly: dramatic improvement with the somatostatin analogue SMS 201-995. 213 20

Ten patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open-label prospective trial of 3 daily subcutaneous injections of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201-995 doses were increased in a stepwise fashion from 100 micrograms every 8 h (three times daily) to 200, 300 and finally 500 micrograms three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12-h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 micrograms t.i.d. in 7/10 patients. Somatomedin-C (SM-C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201-995 up to 500 micrograms three times daily did not produce further clinically relevant GH or SM-C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side-effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 micrograms/day and one patient on 600 micrograms/day after 6-12 months treatment. This dose-finding study shows that 100 micrograms three times daily SMS 201-995 is an effective therapy for most of the acromegalic patients we treated.
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PMID:Clinical and biochemical effects of incremental doses of the long-acting somatostatin analogue SMS 201-995 in ten acromegalic patients. 220 Jun 20

Somatostatin analogue (Sandostatin; SMS 201-995) is utilized as a therapy in acromegaly because of its efficiency in inhibiting GH secretion; it induces some clinical improvements, such as headache remission in acromegalic patient, which seem to be unrelated to Gh normalization. We have examined 8 acromegalic patients, suffering from headache, after injection of saline solution and subsequently of SMS 201-995 (100 y), in order to study the mechanism of analgesic effect induced by Sandostatin administration. Headache, by autovaluation test, heart rate frequency, PAO, sistolic and diastolic blood velocity in medial cerebral artery, by utilizing Transcranial Doppler Sonography (SDSV), have been measured before and after saline and after SMS 201-995. GH and beta-endorphin have been also assayed in plasma samples. All patients have shown a rapid and complete improvement in headache after Sandostatin administration. At the same time we have observed an increase in SDSV and a parallel slight increase in PAO values, more evident in the diastolic phase. Plasma beta-endorphin assay has shown rather conflicting results after SMS 201-995 administration. Our results confirm an important and rapid analgesis effect of Sandostatin on acromegaly headache unrelated to GH normalization. The cerebral emodinamic changes suggest their involvement in Sandostatin induced analgesia.
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PMID:[Analgesic effect of Sandostatin (SMS 201-995) in acromegaly headache]. 227 13

A female is reported with a pituitary tumor secreting growth hormone which remained active and induced invalidating headache in spite of previous treatment with surgery and radiotherapy. Treatment with the sustained action somatostatin analogue, SMS 201-995, was started and headache was improved in a matter of minutes, even if normalization of hormone hypersecretion was not demonstrated. The pathophysiological mechanisms possibly implicated in the improvement are discussed, and this therapeutic option in patients with headache unresponsive to common analgesics is emphasized.
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PMID:[Analgesic effect of a somatostatin analog, SMS 201-995, on headache associated with tumor of the hypophysis]. 262 43

Sixty-four patients with active acromegaly and three patients with gigantism were treated with the long acting somatostatin analog SMS 201-995 (50-500 micrograms, sc, every 6-12 h or 150-880 micrograms daily by intermittent sc infusion, for up to 114 weeks). The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 49 patients and became normal in 18 patients. Suppression of GH secretion was associated with normalization of plasma somatomedin-C levels (14 out of 30 cases) and significant clinical improvement such as disappearance of headache and decrease of excessive sweating. Shrinkage of pituitary tumors as determined by computed tomography and/or magnetic resonance imaging studies occurred in 11 out of 40 cases. Side effects were minimal and tolerable. SMS 201-995 appears to be an effective agent for the treatment of acromegaly and gigantism.
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PMID:[A multicenter clinical trial of SMS 201-995 (octreotide acetate) in acromegaly and gigantism]. 268 94

We studied a 42-year-old woman who had persistent active acromegaly despite conventional therapies. She was treated for 6 months with SMS 201-995. Her mean plasma growth hormone GH values decreased during treatment from 9.1 +/- 1.2 to 6.6 +/- 1.2 micrograms/L. One month after the withdrawal of SMS 201-995, the plasma GH level increased to 24.4 micrograms/L (P less than 0.001). This elevation was clinically silent and transitory, as GH levels decreased 8 months later to 6.9 +/- 1.3 micrograms/L. Furthermore, at the beginning of therapy, her intractable headache was completely relieved; however, it progressively resumed under therapy. In conclusion, cessation of SMS 201-995 may be followed in some acromegalic patients by a rebound of plasma GH levels. This rebound suggests that SMS 201-995 decreases GH levels by an inhibition of its release from the pituitary. Furthermore, SMS 201-995 may relieve intractable headache in some acromegalic patients, but tolerance to the analgesic effect may develop.
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PMID:Growth hormone rebound after cessation of sms 201-995 treatment in acromegaly. 280 8

Fourteen acromegalic patients, half of whom had been unsuccessfully treated with surgery, radiotherapy, or bromocriptine, were given the somatostatin analogue SMS 201-995 parenterally as the sole therapeutic regimen after a single administration had demonstrated suppression of serum growth hormone (GH). An impressive and sustained clinical improvement was documented in all patients, including those in whom bromocriptine had failed; most marked was the decrease in soft tissue swelling and headache and an improved performance status. GH levels decreased each time SMS 201-995 was injected but returned to basal levels within 8 h in most of the patients. With chronic therapy, 24-h mean levels were significantly suppressed, and the GH stimulability of thyrotrophin-releasing hormone and growth-hormone-releasing hormone (pl-44) was markedly reduced. Discontinuation of SMS 201-995 therapy was associated with a return of symptoms and abnormal GH dynamics. The efficacy and safety of chronically administered SMS 201-995 in active acromegaly opens new horizons for its treatment.
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PMID:Therapy of acromegaly with SMS 201-995: long-term studies. 287 99

Six patients with resistant acromegaly were given a long-acting somatostatin analogue (SMS 201-995) for 5 to 12 months. The clinical response was dramatic; relief of headache occurred within minutes of the injection. The mean 24-hour growth hormone levels fell acutely after the administration of 50 or 100 micrograms every 12 hours, especially in four patients with small tumors (p less than 0.001). Dosages of up to 1500 micrograms/d were necessary to produce maximum lowering of growth hormone secretion in some patients. On long-term treatment, plasma somatomedin-C levels fell in all patients and became normal in four. Plasma immunoreactive levels of SMS 201-995 related inversely to growth hormone concentration: A reproducible threshold for growth hormone inhibition in five of the patients, ranging from 70 to 1200 pg/mL, was maintained for 6 to 8 hours after the injections. This somatostatin analogue is effective in the treatment of acromegaly, has no major side effects, and causes only transient changes in carbohydrate metabolism.
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PMID:Treatment of resistant acromegaly with a long-acting somatostatin analogue (SMS 201-995). 287 5

Nine acromegalic patients, six previously untreated, were studied before and after 3-15 months of treatment with a long-acting somatostatin analogue (SMS 201-995; 100 micrograms injected s.c. three times daily). During treatment, the mean (+/- SEM) 24-h GH concentration fell from 82 +/- 22 mIU/l to 33 +/- 7 mIU/l (P less than 0.001), and eight of the 9 patients showed a reduction of at least 50% in GH levels in the fasting state and/or during a glucose tolerance test. There was a significant 30% fall in serum concentrations of insulin-like growth factor (IGF-1) with SMS. All patients showed rapid clinical improvement, with diminished sweating and headaches, and reduction in skinfold thickness, hand volumes and finger size. Computer tomographic scanning of the pituitary in eight patients showed no change in the size of the pituitary tumour during treatment. The only side-effects of SMS noted were transient abdominal discomfort and loose stools in two patients on initiating therapy. Although fasting plasma glucose concentration did not change during treatment (5.4 +/- 0.3 vs 5.5 +/- 0.3 mmol/l), mean 24-h plasma glucose concentration was higher with SMS (6.6 +/- 0.5 mmol/l vs 6.0 +/- 0.4 mmol/l; P less than 0.02). Mean 24-h plasma insulin concentration fell from 87 +/- 11 mIU/l before treatment to 39 +/- 6 mIU/l during treatment (P less than 0.005). No change in other anterior pituitary hormones was observed. SMS appears to be a safe, rapidly effective, long-term treatment for certain patients with acromegaly.
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PMID:Effective long-term treatment of acromegaly with a long-acting somatostatin analogue (SMS 201-995). 287 56


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