Disease relevance of PAPAVERINE HYDROCHLORIDE

• Letter: Papaverine for tardive dyskinesia [1]?
• Acetylcholine (ACH) at graded doses (1, 3, 10 and 30 micrograms/min) and papaverine (10 mg) were selectively infused into the left anterior descending coronary artery of 28 patients, in whom the study artery was angiographically normal (n = 16) or with mild stenosis < or = 40% (n = 12) [2].
• Papaverine-induced maximal increases in coronary blood flow were significantly greater in normals, but no differences were noted between the groups of patients with early atherosclerosis, with hypertension, and with hypercholesterolemia [3].
• In developing a chemotherapeutic program for children with disseminated neuroblastoma, we established three human neuroblastoma lines in cell culture to study the effects of dibutyryl cyclic AMP, papaverine, 5-trifluoromethyl-2'-deoxyuridine, and cyclophosphamide on cell growth, biochemical behavior, and morphology [4].
• Larger doses of intravenous papaverine returned mesenteric blood flow toward control values but caused systemic arterial hypotension [5].

Psychiatry related information on PAPAVERINE HYDROCHLORIDE

• A double-blind, placebo-controlled study was conducted in 20 elderly patients with dementia associated with diffuse cerebrovascular disease to determine the effects of papaverine on the electrical activity of the brain [6].
• The results suggest that measurement of corporal clearance of Tc-RBC after intracorporal injection of papaverine may be a useful method in detecting venous leak, and could be used as a screening test in patients with erectile dysfunction [7].
• In Experiment I, the phosphodiesterase inhibitor papaverine (50 mg/kg), immediately after a one-trial acquisition task, functionally increased cAMP levels and prevented amnesia 3 h after treatment with AMPT (200 mg/kg) for New Zealand A strain (NZ/A) mice tested in a step-through passive avoidance apparatus [8].
• Papaverine is found to inhibit conditioned avoidance responding in rats and mice and to inhibit PCP- and amphetamine-stimulated locomotor activity in rats [9].
• Patients with a history of alcohol abuse or liver disease, however, should be followed up more closely when papaverine is selected for intracavernous injection [10].

High impact information on PAPAVERINE HYDROCHLORIDE

• Papaverine inhibits release and phosphorylation while not strongly influencing shape change, suggesting that shape change does not require phosphorylation [11].
• When added to mouse neuroblastoma cultures, the potent tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) inhibits spontaneous neurite formation as well as that induced in response to serum deprivation, prostaglandin E1, 5-bromo-2'-deoxyuridine, and papaverine [12].
• The administration of papaverine, however, reduced both the slow EPSP and the slow IPSP [13].
• The iliac artery was perfused at constant blood flow and maximal vasodilatation was produced with papaverine [14].
• Resolution of lower limb neurological deficit with penile papaverine in spinal arteriovenous malformation [15].

Chemical compound and disease context of PAPAVERINE HYDROCHLORIDE

• The ZL decreased significantly (P less than 0.01) from the pre- to post-bypass conditions (with and without the stenosis), at steady-state and after papaverine hydrochloride administration [16].
• The duration of hyperemia was much shorter after adenosine than after papaverine administration [17].
• Topical application of papaverine and nitroglycerin proximal to the stenosis did not abolish the cyclic flow reduction, although a transient fall in systemic pressure indicated that they had been absorbed [18].
• At maximal hyperemia, mean arterial blood pressure fell 9 +/- 2% (mean +/- SEM) after intracoronary papaverine, 8 +/- 4% after dipyridamole, and 3 +/- 3% after meglumine diatrizoate [19].
• In addition, after papaverine bolus injections, flow increased by 114 +/- 8% versus baseline, and ascorbyl levels increased by 5.4 +/- 0.7 nmol/L (n = 31, P < .001); similar results occurred with adenosine, isoproterenol, or hyperemia after 30-second occlusions (P < .05, n = 4 or 5 in each group) [20].

Biological context of PAPAVERINE HYDROCHLORIDE

• However, the same dose of papaverine given intravenously to other dogs was ineffective in correcting the deranged hemodynamics and oxygen kinetics [5].
• Penile erection elicited by papaverine is reduced profoundly in mice with targeted deletion of eNOS [21].
• Measurements of epicardial arterial cross-sectional area (ECA), velocity, estimated flow (velocity times area), and vascular resistance were made before and after bolus administration of acetylcholine (100 micrograms i.c.). Similar measurements were made after papaverine (12-15 mg i.c.), a nonendothelium-dependent vasodilator [22].
• Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram [17].
• Cilostamide, Ro 15-2041, milrinone, papaverine, isobutylmethylxanthine, and theophylline inhibited the 110-kDa platelet enzyme with IC50 values of 0.04, 0.13, 0.46, 1.4, 2.6, and 110 microM, respectively [23].

Anatomical context of PAPAVERINE HYDROCHLORIDE

• Papaverine relaxes smooth muscle from various organ systems throughout the body [24].
• Papaverine, infused into the cephalic (superior) mesenteric artery at an average dose of 100 micrograms/kg X min, was completely effective in restoring mesenteric blood flow and correcting altered intestinal oxygen kinetics [5].
• The purpose of this study was to determine the effects of papaverine on colonic smooth muscle from the transverse colon of the cat [24].
• Perfusion pressure was then determined in the hindlimbs of pithed rats under conditions of constant blood flow (4.0 ml/min) and maximal vasodilation (hemodilution to 22% hematocrit combined with continuous nitroprusside and papaverine infusion) [25].
• Regional myocardial perfusion and CR were assessed at baseline and after LAD papaverine (10-12 mg) by means of two microsphere injections in the left ventricle and compared with five normal subjects [26].

Associations of PAPAVERINE HYDROCHLORIDE with other chemical compounds

• In control subjects, dilation was observed in response to atrial pacing (8.7 +/- 7.6%; P < .05), CPT (8.8 +/- 2.3%; P < .01), exercise (14.5 +/- 9.4%; P < .001), and papaverine infusion (14.2 +/- 6.1%; P < .001) and after injection of SIN-1 (26.8 +/- 11.9%; P < .001) [27].
• This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model [28].
• In contrast, coronary blood flow reserve to the endothelium-independent smooth muscle relaxant papaverine was similar in the two groups [29].
• We compared the coronary vasodilation resulting from infusion of the standard dose of dipyridamole with that resulting from a maximally dilating dose of intracoronary papaverine in 12 patients with angiographically normal coronary arteries [30].
• In contrast, the vasodilation elicited by topical papaverine (1 mM) was not affected by N omega-nitro-L-arginine (n = 10) [31].

Gene context of PAPAVERINE HYDROCHLORIDE

• Both electrical stimulation of the cavernous nerve and direct intracavernosal injection of the vasorelaxant drug papaverine cause rapid increases in phosphorylated (activated) Akt and eNOS [21].
• Chronic administration of the phosphodiesterase (PDE) inhibitors rolipram or papaverine also increased expression of CREB mRNA in hippocampus, demonstrating a role for the cAMP cascade [32].
• In vivo, OT intra-cavernous injection (ICI) dose-dependently inhibited intracavernous pressure (ICP) increase elicited by either electrical stimulation of the cavernous nerve or ICI of papaverine with similar IC(50)s (117.7 +/- 37 mU) [33].
• Moreover, endothelin-1 did not markedly change the inhibitory effects of papaverine (0.1-100 microM) or isoprenaline (1 nM-100 microM) on responses to electrical field stimulation [34].
• Relaxation to nitroprusside and papaverine was similar in arteries from both IL-10 -/- and IL-10 +/+ mice after vehicle or LPS injection [35].

Analytical, diagnostic and therapeutic context of PAPAVERINE HYDROCHLORIDE

• CR (papaverine/resting perfusion) was 3.8 +/- 0.2 and 1.51 +/- 0.27 in normal subjects and in ischemic patients, respectively (p < 0.01) [26].
• This effect was paralleled by an almost 4-fold increase in forearm blood flow (FBF), whereas an equieffective dose of papaverine produced no change in venous NO(2)-. Intraarterial infusion of NO(2)- had no effect on FBF [36].
• Both increased after angioplasty to 3.65 +/- 0.57 and 3.36 +/- 0.70, respectively (P < .05) [37].
• The coronary blood flow velocity at rest and in response to a hyperemic dose of papaverine was measured [38].
• Maximal vasodilation was induced immediately before and 15 minutes after PTCA by intracoronary administration of papaverine, and digital angiographic studies were performed [39].

References