Abstract：
:The role of flexibility of the alkyl side chain in the tetrahydrocannabinols to cannabinoid activity has been delineated in previous studies with side chain analogs of Delta(8)-tetrahydrocannabinol with double or triple bonds. This study investigated the site of antinociceptive action for these analogs through analysis of structure-activity relationships following different routes of administration. In analogs without terminal substitutions, potency was greater following intrathecal (i. t.) injection than with intracerebroventricular (i.c.v.). Further, optimal structural features differed for each route of administration. Absolute position of the double or triple bond best predicted i.t. potency. In contrast, i.c.v. potency was best predicted by the size of the alkyl substituent beyond the point of unsaturation. Terminal substitutions tended to increase i.c.v. potency while decreasing or not affecting i.t. These results suggest that receptor mechanisms for cannabinoid antinociceptive effects differ in brain and spinal cord, although potential pharmacokinetic differences in rate of local distribution cannot be eliminated.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Wiley JL,Patrick GS,Crocker PC,Saha B,Razdan RK,Martin BRdoi
10.1016/s0014-2999(00)00259-4keywords:
subject
Has Abstractpub_date
2000-06-02 00:00:00pages
319-26issue
2-3eissn
0014-2999issn
1879-0712pii
S0014299900002594journal_volume
397pub_type
杂志文章abstract：:Leukocytes can generate a substance that, when added to some partially purified human kininogen, is capable of forming kinins. The addition of endotoxin or polystyrene latex particles to the incubated leukocytes doubled the amount of kinin generated. Certain preparations of kininogen, however, failed to allow kinin fo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90137-5
更新日期：1975-08-01 00:00:00
abstract：:The alpha 1-adrenoceptor agonist, SDZ NVI-085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4- methyl-9-(methylthio)-2H-naphth[2,3-b]-1,4-oxazine.HCl; 1 mg/kg i.p.), decreased body temperature of guinea-pigs. Two 5-HT1D receptor antagonists, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00526-q
更新日期：1995-10-24 00:00:00
abstract：:The response of lymph vessels, arterioles and venules in the exteriorized rat mesentery to endothelin-1, vasopressin and norepinephrine was examined with the aid of high-resolution television microscopy. On a molar basis, endothelin-1 was more potent than vasopressin to contract the three types of vessels. Norepinephr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90135-0
更新日期：1989-10-24 00:00:00
abstract：:The contractile actions of imidazoline alpha-adrenoceptor agonists were investigated in human vas deferens longitudinal and circular muscle. The effects of phenoxybenzamine were studied in comparison to dibenamine and SZL-49 (4-amino-6,7-dimethoxy-2-quinazolinyl-4-(2-bicyclo[2,2,2]octa-2,5-dienylcarbonyl-2-piperazine)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01346-3
更新日期：2003-02-21 00:00:00
abstract：:Prior studies demonstrated that guanabenz reduces systemic blood pressure by inhibiting central sympathetic outflow as well as by adrenergic neuron blockade. Potential mechanisms responsible for the reduction of efferent sympathetic activity were examined in the present series. Guanabenz failed to modify carotid sinus...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90005-4
更新日期：1976-05-01 00:00:00
abstract：:The aim of the present study was to examine the influence of ifenprodil (a non-competitive NMDA receptor antagonist which also blocks 5-HT3 receptors and alpha1-adrenoceptors) on the effects of ethanol in the mouse in vivo and to elucidate the role of various receptors in these actions. The ethanol (4 g/kg i.p.)-induc...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00393-3
更新日期：1999-07-14 00:00:00
abstract：:To investigate the mechanism underlying sulpiride-induced catalepsy, we simultaneously examined cataleptic behavior and the kinetics of the dopamine receptor antagonist, sulpiride of dopamine, and the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), using in vivo voltammetry. After intrastriatal administrat...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)00140-4
更新日期：1997-05-12 00:00:00
abstract：:Recent evidence suggests that polydatin (PD), a resveratrol glucoside, may have beneficial actions on the cardiac hypertrophy. Therefore, the current study focused on the underlying mechanism of the PD anti-hypertrophic effect in cultured cardiomyocytes and in progression from cardiac hypertrophy to heart failure in v...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.11.012
更新日期：2015-01-05 00:00:00
abstract：:Purinergic P2Y-receptor agonists amplify glucose-induced insulin secretion from pancreatic beta-cells, thus offering new opportunities for the treatment of type 2 diabetes. However, little is known about which subtypes of purinergic P2Y receptors are expressed in these cells. The INS-1 beta-cell line is used as a mode...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.04.012
更新日期：2007-07-30 00:00:00
abstract：:NP-252, a new dihydropyridine derivative, and nifedipine non-competitively inhibited contractile responses to KCl and responses to Ca2+ in Ca(2+)-free medium containing KCl in rabbit aorta and renal, mesenteric, coronary and basilar arteries, mesenteric veins and vena cava. The effects of NP-252 in these smaller arter...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90888-w
更新日期：1991-10-22 00:00:00
abstract：:Amitriptyline is known to increase the permeability of the blood-brain barrier but the morphological basis of this increase has not been studied. As catecholamines can influence pinocytosis in dog peripheral blood vessels, the effect of amitriptyline on the pinocytotic activity of blood brain microvessels was studied....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90133-q
更新日期：1990-01-25 00:00:00
abstract：:Pregabalin, a ligand of alpha(2)delta subunits of voltage-gated calcium channels, reduces visceral hypersensitivity associated with irritable bowel syndrome. However, effects of pregabalin on bowel function are not well described. We investigated the effects of pregabalin on bowel dysfunction and colonic nociceptive t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.06.014
更新日期：2010-09-15 00:00:00
abstract：:High stereoselectivity was observed for the enantiomers of trihexyphenidyl and trihexyphenidyl methiodide at muscarinic M1-receptors in field-stimulated rabbit vas deferens and at M2 alpha- and M2 beta-receptors in guinea-pig atrium and ileum, respectively. Considerably higher affinities (up to 1700-fold) were found f...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90417-7
更新日期：1988-10-11 00:00:00
abstract：:In human bronchial rings the thromboxane A2 (TxA2) mimetic, U46619, produced cumulative concentration-related contractions up to a maximum of 141 +/- 23% of the response induced by carbachol or acetylcholine. The geometric mean EC50 value was 3.2 X 10(-8) M (95% confidence interval: 1.2, 8.9 X 10(-8) M) (n = 5). Contr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90715-2
更新日期：1989-06-20 00:00:00
abstract：:The recent elucidation of the primary structures of different melatonin receptors as well as the deduction of the secondary structure of rhodopsin has allowed us to construct a model for melatonin recognition at its G protein-coupled receptor. To achieve this, we have used the quantum mechanics method Austin model 1 t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00114-8
更新日期：1996-05-23 00:00:00
abstract：:Renal mesangial cells exposed to inflammatory cytokines produce high concentrations of nitric oxide (NO) which may exert cytotoxic actions. We report here that glomerular mesangial cells, endothelial cells and epithelial cells in culture are themselves targets for NO and undergo apoptotic cell death upon exposure to h...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(96)00701-7
更新日期：1996-12-12 00:00:00
abstract：:Using microscopic fluorometry and fura-2-loaded cultured bovine aortic endothelial cells, we determined the effects of captopril, an angiotensin converting enzyme (ACE) inhibitor, on bradykinin-induced Ca2+ transients in endothelial cells. In the presence of extracellular Ca2+, 10(-9) M bradykinin induced an early ris...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(93)90018-5
更新日期：1993-01-15 00:00:00
abstract：:Ascorbate has both antioxidant and pro-oxidant activities. We have previously shown that plasma levels of ascorbate induce constriction and blockade of dilatation mediated by endothelium-derived hyperpolarizing factor (EDHF). In this study we sought to determine if these detrimental actions were mediated by a prooxida...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.04.033
更新日期：2009-07-01 00:00:00
abstract：:The effect of prolonged administration of high doses of buspirone on its 5-hydroxytryptamine (5-HT) release-inhibitory and anxiolytic-like properties was investigated. The 5-HT release-inhibitory effect of a challenge dose of buspirone (0.5 mg/kg, s.c.) was identical in rats chronically treated with vehicle or buspiro...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90977-p
更新日期：1993-08-03 00:00:00
abstract：:In adult male rats, injection of TRH into a lateral ventricle of the brain 5 min prior to pentobarbital (PB) administration caused a significant dose-related inhibition of prolactin (PRL) release, in doses ranging from 500 to 5 ng. Among 8 TRH analogues devoid of thyrotropin-releasing activity, 6 were found to signifi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90276-x
更新日期：1977-10-15 00:00:00
abstract：:We investigated the involvement of dopamine D1 and D2 receptor subtypes in the effects of GBR 12909, a selective dopamine uptake inhibitor, on latent learning in the performance of a water-finding task and on locomotor activity in mice. GBR 12909 (10 and 20 mg/kg) impaired latent learning, and this effect was countera...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90949-i
更新日期：1993-04-06 00:00:00
abstract：:The mechanisms of 12(S)-hydroperoxyeicosa-5Z,8Z,10E,14Z-tetraenoic acid (12(S)-HPETE)-induced scratching were studied in ICR mice. In a recent paper, we demonstrated that the 12(S)-HPETE-induced scratching was reduced not by U75302 (BLT(1) receptor antagonist), but by LY255283 (BLT(2) receptor antagonist). In the pres...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.11.005
更新日期：2008-01-28 00:00:00
abstract：:To determine whether a mu opioid agonist modulates the effects of a kappa opioid agonist in squirrel monkeys responding under a shock titration procedure, morphine was administered in combination with an ED75 dose of U50,488. Morphine (0.03-0.3 mg/kg) did not alter U50,488's early peak effects (15-25 min post-injectio...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90954-g
更新日期：1993-04-06 00:00:00
abstract：:The effect of xanthone on smooth muscle was studied in thoracic aorta isolated from rats. Xanthone relaxed the norepinephrine-induced contraction of rat thoracic aorta. This relaxing effect of xanthone persisted in endothelium-denuded aorta suggesting that the relaxation induced by xanthone is endothelium-independent....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01224-7
更新日期：1997-10-01 00:00:00
abstract：:The corticotropin releasing factor (CRF) family includes CRF and urocortin. The effects of urocortin and CRF (0.3, 1, 3 and 10 nmol/kg, i.v.) relative to those of vehicle (0.9% NaCl) on mean arterial pressure and mean circulatory filling pressure (index of venous tone) were examined in conscious, unrestrained rats tha...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.01.022
更新日期：2005-03-07 00:00:00
abstract：:The new platinum (II) and palladium (II) complexes (2-4) with ligands 5-(2-hydroxyphenyl)-1,3-dimethyl-4-(dimethoxy)phosphonyl-1H]-pyrazole (1a) and 5-(2-hydroxyphenyl)-1,3-dimethyl-4-methoxycarbonyl-1H]-2-pyrazole (1b) were screened in a search for novel anticancer agents. Thus, alkylating activity, cytotoxicity, abi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.08.053
更新日期：2004-10-11 00:00:00
abstract：:A single dose of methamphetamine (25 mg/kg i.p.) was administered to young adult gerbils (Meriones unguiculatus) aged 90 days and the number of spices was determined along 40-microns segments of basal, lateral and apical dendrites of pyramidal cells in layers III and V of the prefrontal cortex, after 1.5, 7, 20 and 30...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90937-d
更新日期：1993-09-07 00:00:00
abstract：:The effects of group 2- versus group 3-selective metabotropic glutamate (mGlu) receptor agonists were examined against forskolin (10 microM)-, vasoactive intestinal peptide (VIP; 1 microM)- and 5'-N-ethylcarboxamidoadenosine (NECA; 10 microM)-stimulated cAMP accumulations in adult rat hippocampal slices (in the presen...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00747-4
更新日期：1996-02-22 00:00:00
abstract：:The site of action of the kappa opioid receptor agonist, U-50,488H in suppressing the development of tolerance to morphine antinociception was examined by local application, either intrathecal (i.t., spinal) or intracerebroventricular (i.c.v., supraspinal) in mice. Mice given morphine s.c., i.c.v. or i.t. daily develo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90585-e
更新日期：1991-08-06 00:00:00
abstract：:Infusion of arachidonic acid through the guinea pig lung or the cat spleen causes a release of thromboxane A2 and prostaglandins, as measured by bioassay. After incubation of human platelets with arachidonate similar metabolites are formed, as demonstrated chromatographically. Infusion of imidazole (50-75 microgram/ml...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(77)90104-2
更新日期：1977-07-15 00:00:00
