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British Journal of Clinical Pharmacology Aug 19761 The interaction of phentolamine with the beta-adrenoreceptor-blocking drug, oxprenolol, was studied in a controlled trial. 2 The combination was generally well... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
1 The interaction of phentolamine with the beta-adrenoreceptor-blocking drug, oxprenolol, was studied in a controlled trial. 2 The combination was generally well tolerated. 3 Oxprenolol alone produced modest but significant reductions in supine, standing and post-exercise blood pressures. Small reductions were observed only with sustained phentolamine administration. 4 The combined effect of the two drugs seemed to be addictive only at the lower level of oxyprenolol dosage. 5 Labetalol produced significantly greater reductions in supine and standing blood pressure than combined oxprenolol-phentolamine. At a daily dose of 400 mg, postural hypotension was not observed, although transient symptoms were frequent.
Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Evaluation; Drug Synergism; Drug Therapy, Combination; Ethanolamines; Female; Heart Rate; Humans; Hypertension; Labetalol; Male; Middle Aged; Oxprenolol; Phentolamine
PubMed: 791332
DOI: No ID Found -
The American Journal of Case Reports Sep 2020BACKGROUND Accidental finger-stick injuries have been reported with epinephrine autoinjectors, such as EpiPen and EpiPen Jr, and can result in necrosis and digital...
BACKGROUND Accidental finger-stick injuries have been reported with epinephrine autoinjectors, such as EpiPen and EpiPen Jr, and can result in necrosis and digital ischemia. However, long-term adverse effects are very rare. The treatment for accidental finger-stick injuries is controversial and includes intra-arterial injections of vasodilating agents, topical vasodilators, and supportive management as needed. CASE REPORT Here, we report a case of a 26-year-old pharmacist who injected herself accidentally with an EpiPen on the tip of her index finger. Warm water and nitroglycerine gel did not alleviate her symptoms. After three hours, phentolamine was injected around the necrotic area, and the skin normalized. CONCLUSIONS All health professionals should be trained in how to handle epinephrine autoinjectors safely. Phentolamine may be efficacious in treating accidental finger-stick injuries from epinephrine autoinjectors.
Topics: Adult; Epinephrine; Female; Finger Injuries; Humans; Injections; Ischemia; Needlestick Injuries; Phentolamine
PubMed: 32921785
DOI: 10.12659/AJCR.923877 -
British Medical Journal Jun 1971
Topics: Abdomen; Aged; Female; Gases; Gastrointestinal Motility; Guanethidine; Humans; Intestinal Obstruction; Intestines; Neostigmine; Phentolamine; Postoperative Complications
PubMed: 5090757
DOI: No ID Found -
PloS One 2018A tetrodotoxin (TTX)-resistant mechanism is responsible for the electrical field stimulation (EFS)-induced contractions and relaxations of Crotalus durissus terrificus...
A tetrodotoxin (TTX)-resistant mechanism is responsible for the electrical field stimulation (EFS)-induced contractions and relaxations of Crotalus durissus terrificus corpora cavernosa. Here it was investigated whether this mechanism also occurs in corpora cavernosa and aortae of the non-venomous snake Pantherophis guttatus corpora cavernosa and aortae. Corpora cavernosa and aortic rings isolated from Pantherophis guttatus snake were mounted in organ bath system for isometric tension recording. EFS-induced contractions in both tissues were performed in the presence and absence of guanethidine (30 μM), phentolamine (10 μM) and tetrodotoxin (1 μM). In another set of experiments, the endothelium was removed from aortic rings and EFS-induced contractions were performed in the denuded rings. Electrical field stimulation-induced contractions were frequency-dependent in Pantherophis guttatus corpora cavernosa and aortic rings. The contractions were significantly reduced in the presence of guanethidine (30 μM) or phentolamine (10 μM). Pre-treatment with tetrodotoxin had no effect on the EFS-induced contractions of either corpora cavernosa or aortic rings. Surprisingly, the EFS-induced contractions of aortic rings denuded of endothelium were almost abolished. These results indicate that the TTX-resistant mechanism is present in EFS-induced contractions of Pantherophis guttatus corpora cavernosa and aortae. The experiments performed in the aorta indicate that the endothelium is the main source for the release of catecholamines induced by EFS.
Topics: Acetylcholine; Animals; Electric Stimulation; Endothelium, Vascular; Muscle Contraction; Phentolamine; Snakes; Tetrodotoxin
PubMed: 29672643
DOI: 10.1371/journal.pone.0196123 -
Physiological Research May 2018Electric stimulation (ES) could induce contraction of intestinal smooth muscle. The aim of this study was to analyze the effects of ES on esophageal motility and the...
Electric stimulation (ES) could induce contraction of intestinal smooth muscle. The aim of this study was to analyze the effects of ES on esophageal motility and the underlying mechanism in vivo. Twenty-eight rabbits were equipped with a pair of subserosa electrodes (connected to an electrical stimulator) in the lower segment of the esophagus. The ES signal consisted of bipolar rectangular pulse trains, lasting for 3 s, with different amplitudes (1 mA, 3 mA, 5 mA and 10 mA), and frequencies (10 Hz, 20 Hz and 50 Hz). The amplitude of the contraction was recognized by high-resolution manometry. The effect of ES was tested under anesthesia and following administration of atropine, phentolamine or L-NAME. ES induced esophageal contraction at the stimulated site. A statistically significant increase in esophageal pressure was observed when the stimulation amplitude was above 3 mA. The increase in esophageal pressure was associated with the amplitude of stimulus as well as the frequency. During stimulation, atropine, phentolamine and L-NAME had no effect on the increase of esophageal pressure induced by ES. These findings implied that ES induced esophageal contraction were not mediated via the NANC, adrenergic or cholinergic pathway. The amplitude of esophageal contraction was current and frequency dependent.
Topics: Adrenergic alpha-Antagonists; Animals; Atropine; Electric Stimulation; Esophageal Motility Disorders; Esophagus; Gastrointestinal Motility; Male; Manometry; Muscarinic Antagonists; Muscle Contraction; NG-Nitroarginine Methyl Ester; Phentolamine; Rabbits
PubMed: 29303604
DOI: 10.33549/physiolres.933652 -
British Journal of Pharmacology Sep 19901. The effects of phentolamine and yohimbine on adenosine 5'-triphosphate (ATP)-sensitive K+ channels were studied in normal mouse beta-cells. 2. In the presence of 3 mM...
1. The effects of phentolamine and yohimbine on adenosine 5'-triphosphate (ATP)-sensitive K+ channels were studied in normal mouse beta-cells. 2. In the presence of 3 mM glucose, many ATP-sensitive K+ channels are open in the beta-cell membrane. Under these conditions, phentolamine inhibited 86Rb efflux from the islets. This inhibition was faster with 100 than with 20 microM phentolamine but its steady-state magnitude was similar with both concentrations. Yohimbine (20-100 microM) also inhibited the efflux rate but was not as potent as phentolamine. 3. In the presence of 6 mM glucose, most ATP-sensitive K+ channels are closed in the beta-cell membrane. Their opening by 100 microM diazoxide caused a marked acceleration of 86Rb efflux from the islets. This acceleration was almost entirely prevented by 20 microM phentolamine. It was barely affected by 20 microM yohimbine and reduced by 50% by 100 microM yohimbine. 4. ATP-sensitive K+ currents were studied in single beta-cells by the whole cell patch-clamp technique. Phentolamine (20-100 microM) caused a progressive but almost complete and irreversible inhibition of the current. The effects of yohimbine were faster but smaller; the inhibition was still incomplete with 100 microM yohimbine. 5. The increase in ATP-sensitive K+ current produced by 100 microM diazoxide was prevented by 100 microM phentolamine but only partially attenuated by 100 microM yohimbine. 6. It is concluded that phentolamine inhibits ATP-sensitive K+ channels in pancreatic beta-cells. This novel effect of phentolamine resembles that of hypoglycaemic sulphonylureas. It may account for previously unexplained effects of the drug. These observations also call for reinterpretation of many studies in which phentolamine was used as an allegedly specific blocker of alpha-adrenoceptors.
Topics: Adenosine Triphosphate; Animals; Diazoxide; Female; In Vitro Techniques; Islets of Langerhans; Mice; Phentolamine; Potassium Channels; Rubidium Radioisotopes; Tolbutamide; Yohimbine
PubMed: 2282453
DOI: 10.1111/j.1476-5381.1990.tb12099.x -
BMC Ophthalmology Oct 2022Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD.
METHODS
In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed.
RESULTS
Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia.
CONCLUSION
PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD.
TRIAL REGISTRATION
The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.
Topics: Adult; Contrast Sensitivity; Female; Glare; Humans; Hyperemia; Male; Middle Aged; Night Blindness; Night Vision; Ophthalmic Solutions; Phentolamine; Vision Disorders
PubMed: 36209072
DOI: 10.1186/s12886-022-02621-6 -
PloS One 2013Using pairings of male crayfish Procambarus clarkii with a 3-7% difference in size, we confirmed that physically larger crayfish were more likely to win encounters...
Using pairings of male crayfish Procambarus clarkii with a 3-7% difference in size, we confirmed that physically larger crayfish were more likely to win encounters (winning probability of over 80%). Despite a physical disadvantage, small winners of the first pairings were more likely to win their subsequent conflicts with larger naive animals (winning probability was about 70%). By contrast, the losers of the first pairings rarely won their subsequent conflicts with smaller naive animals (winning probability of 6%). These winner and loser effects were mimicked by injection of serotonin and octopamine. Serotonin-injected naive small crayfish were more likely to win in pairings with untreated larger naive crayfish (winning probability of over 60%), while octopamine-injected naive large animals were beaten by untreated smaller naive animals (winning probability of 20%). Furthermore, the winner effects of dominant crayfish were cancelled by the injection of mianserin, an antagonist of serotonin receptors and were reinforced by the injection of fluoxetin, serotonin reuptake inhibitor, just after the establishment of social order of the first pairings. Injection of octopamine channel blockers, phentolamine and epinastine, by contrast, cancelled the loser effects. These results strongly suggested that serotonin and octopamine were responsible for winner and loser effects, respectively.
Topics: Agonistic Behavior; Animals; Astacoidea; Behavior, Animal; Biogenic Amines; Body Size; Injections; Male; Mianserin; Octopamine; Phentolamine; Serotonin; Social Dominance
PubMed: 24058575
DOI: 10.1371/journal.pone.0074489 -
Zhongguo Yao Li Xue Bao = Acta... Mar 1998To study the effect of phentolamine on L-type calcium currents (ICa) and ATP-sensitive K+ currents (IK,ATP) in ventricular myocytes.
AIM
To study the effect of phentolamine on L-type calcium currents (ICa) and ATP-sensitive K+ currents (IK,ATP) in ventricular myocytes.
METHODS
ICa and IK,ATP were observed using patch clamp techniques in whole-cell recording configuration.
RESULTS
Phentolamine reduced ICa of ventricular myocytes in concentration-dependent and voltage-independent manners. Phentolamine 5, 25, and 100 mumol.L-1 decreased ICa from 370 +/- 99 nA to 310 +/- 95 nA (17% block, n = 6, P < 0.01), from 230 +/- 98 nA to 180 +/- 73 nA (23% block, n = 5, P < 0.05), and from 293 +/- 66 nA to 206 +/- 44 nA (30% block, n = 5, P < 0.01), respectively, without affecting the current-voltage relationship. Prazosin 100 mumol.L-1 and yohimbine 100 mumol.L-1, which were specific blockers of alpha 1 and alpha 2 adrenoceptors respectively, did not show the inhibitory effect on ICa. Phentolamine 100 mumol.L-1 also inhibited the IK,ATP induced by 2, 4-dinitrophenol (DNP) at 0 mV from 3.2 +/- 0.6 nA to 0.8 +/- 0.5 nA (75% block, n = 4, P < 0.01).
CONCLUSION
Phentolamine directly inhibits ICa and IK,ATP in guinea pig ventricular myocytes.
Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Antagonists; Animals; Calcium Channels; Cells, Cultured; Dose-Response Relationship, Drug; Guinea Pigs; Heart Ventricles; Myocardium; Patch-Clamp Techniques; Phentolamine; Potassium Channels; Prazosin; Yohimbine
PubMed: 10374641
DOI: No ID Found -
Pain Jan 1996Systemic phentolamine administration has been suggested as a diagnostic tool for identifying patients with sympathetically maintained pain (SMP) (Raja et al. 1991). The... (Clinical Trial)
Clinical Trial
Systemic phentolamine administration has been suggested as a diagnostic tool for identifying patients with sympathetically maintained pain (SMP) (Raja et al. 1991). The dose of phentolamine to produce adequate blockade of peripheral alpha-adrenoceptor function has, however, not been previously determined. In this study, the effects of two different doses of phentolamine on peripheral sympathetic vasoconstrictor function were investigated. One-hundred and seventeen (117) patients with chronic extremity pain underwent 130 phentolamine diagnostic tests using two different doses of phentolamine (0.5 mg/kg over 20 min (n = 60) and 1 mg/kg over 10 min (n = 59)). Eleven (11) patients did not receive phentolamine during the test. Cutaneous temperature was measured in the distal extremity before and after administration of phentolamine. In a subset of patients, baseline blood flow and sympathetically mediated vasoconstrictor response (SMR) to deep inhalation were measured on glabrous skin using laser Doppler flowmetry. SMR was elicited with a 5-sec maximal inspiratory gasp. A dose-related increase in cutaneous temperature was observed. In addition, baseline blood flow increased and SMR was attenuated after both doses of phentolamine, but to a greater degree after the 1 mg/kg dose. However, SMR was not completely attenuated, even after administration of the higher phentolamine dose. These results indicate that a phentolamine dose of 1 mg/kg over 10 min more completely blocks alpha-adrenoceptor function than a dose of 0.5 mg/kg over 20 min. We therefore recommend that to ensure adequate alpha-adrenoceptor blockade the higher phentolamine dose be used in the phentolamine diagnostic test for SMP.
Topics: Adolescent; Adrenergic alpha-Antagonists; Adult; Aged; Chronic Disease; Dose-Response Relationship, Drug; Extremities; Female; Humans; Male; Middle Aged; Pain; Phentolamine; Regional Blood Flow; Respiration; Skin; Skin Temperature; Sympathetic Nervous System; Vasoconstriction
PubMed: 8867263
DOI: 10.1016/0304-3959(95)00099-2