1,721,092 research outputs found
A2A receptor ligands: Past, present and future trends
No full textThe adenosine A(2A) receptor is a member of the G protein-coupled receptor family and mediates multiple physiological effects of adenosine, both at the central nervous system and at peripheral tissues. Increasing evidence relates the A(2A) receptor with several pathological conditions such as neurodegenerative disorders, inflammation, pharmacological stress, and wound healing renewing the interest in A(2A) receptor agonists and antagonists as promising leads for drugs. However some of them initially tested in clinical trials presented several side effects, short half-life, lower solubility, and in some cases a lack of effects, perhaps attributable to receptor desensitization or to low receptor density in the targeted tissue. For these reasons it is evident that additional rational chemical modifications of the existing A(2A) receptor ligands to improve their affinity/selectivity and bioavailability as well as further studies to get new template for A(2A)AR ligands are necessary. The purpose of this review is to analyze and summarize the past and the present aspects related to the medicinal chemistry of A(2A) receptor ligands. Moreover their current and possible therapeutic applications have been also highlighted
PHARMACOKINETICS OF TRAMADOL AFTER EPIDURAL ADMINISTRATION IN HORSES
No full textTramadol is a centrally acting analgesic structurally related to codeine and morphine. The aim of the present study was to evaluate the pharmacokinetic of tramadol and its major metabolites after caudal epidural administration in the horse. Six gelding male adult horses were assigned to receive epidural administration of tramadol at 2 mg/kg. Plasma substances detection was achieved using a HPLC-FL method. Tramadol was detectable after 5 minutes up to 8 hours after epidural administration. Metabolites plasma concentrations were found under the limit of quantification of the method; however negligible amounts of M2 was detected from 30 min up to 1 hour in three subjects. In conclusion, this study shows that tramadol administered by caudal route in horses produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to provide analgesia. Further study of the drug's safety and efficacy for the treatment of pain in horses is warranted
Synthesis and pharmacological evaluation of new biphenylic derivatives as CB2 receptor ligands
Full text linkTargeting type-2 cannabinoid receptor (CB2) is considered a feasible strategy to develop new drugs for the treatment of diseases like neuropathic pain, chronic inflammation, neurodegenerative disorders and cancer. Such drugs are devoid of the undesired central side effects that are typically mediated by the CB1 receptor. In this work we synthesized 18 biphenylic carboxamides as new CB2-selective ligands and evaluated their pharmacological profiles. The functional activity of these compounds is strongly influenced by the nature of the substituent at position 4' and 5 of the biphenyl scaffold. Position 5 seems to be responsible for the agonist or inverse agonist behaviour independently of the substituent in position 4', with the exception of the methoxyl group which transforms both full agonists and inverse agonists into neutral antagonists. This study provides a novel complete toolbox of CB2 functional modulators that derive from the same chemical scaffold. Such probes may be useful to investigate the biological role of CB2 receptors in cellular assays
PHARMACOKINETIC EVALUATION OF TRAMADOL AND ITS MAJOR METABOLITES AFTER SINGLE ORAL SUSTAINED TABLET ADMINISTRATION IN THE DOG: A PILOT STUDY
No full textThe study evaluated the pharmacokinetics of tramadol and its major metabolites O-desmethyltramadol (M1), N-desmethyltramadol
(M2) and N–O didesmethyltramadol (M5) following a single oral administration of a sustained release (SR) 100 mg tablet to dogs.
Plasma tramadol concentration was greater than the limit of quantification (LOQ) in three dogs, M1 was quantified only in one dog
while M2 and M5 were quantified in all of the dogs. The median values of Cmax (maximum plasma concentration), Tmax (time to maximum
plasma concentration) and T1/2 (half-life) for tramadol were 0.04 (0.17–0.02) lg mL1, 3 (4–2) and 1.88 (2.211–1.435) h, respectively.
M5 showed median values of Cmax, Tmax and T1/2 of 0.1 (0.19–0.09) lg mL1, 2 (3–1) and 4.230 (6.583–1.847) h, respectively. M2
showed median values of Cmax, Tmax and T1/2 of 0.22 (0.330–0.080) lg mL1, 4 (7–3) and 4.487 (6.395–1.563) h, respectively. The findings
suggest that the SR formulation of tramadol may not have suitable pharmacokinetic characteristics to be administered once-a-day as an
effective and safe treatment for pain in the dog
PHARMACOKINETIC OF TRAMADOL AND ITS MAJOR CONJUGATES AFTER SINGLE PER OS ADMINISTRATION OF THE SUSTAINED TABLET AND PER RECTUM SUPPOSITORIES FORMULATIONS IN DOGS
No full textThe aim of the present study is to evaluate the pharmacokinetics of T and its major metabolites M1, M2 and M5 after the single oral administration of an SR tablet and rectal suppositories in dogs (4-6 mg•kg-1 m.c.). The plasma concentration data after SR-tablet and rectal administration were fitted on the basis of a mono- and non-compartmental model, respectively. T plasma concentration after SR tablet administration was quantitatively detected in three dogs, M1 was quantized in only one dog while M2 and M5 were quantized in all the dogs. T showed median values of Cmax, Tmax and T1/2 of 40 (20-170) ng•mL-1, 3 (4-2) and 1.88 (2.21-1.44) hours, respectively. M5 showed median values of Cmax, Tmax and T1/2 of 0.1 (90-190) ng•mL-1, 2 (3-1) and 4.23 (6.58-1.85) hours, respectively. M2 showed median values of Cmax, Tmax and T1/2 of 220 (80-330) ng•mL-1, 4 (7-3) and 4.49 (6.39-1.57) hours, respectively. Following rectal administration, T was detected from 5 minutes up to 10 h in a smaller amount than M5 and M2. T median value of Cmax was 140±60 ng•mL-1 in 0.56±0.41 h (Tmax). K01 t1/2 and K10 t1/2 were 0.27±0.25 h and 2.24±1.82h, respectively. M1 was detectable from 5 min up to 2 h, showing low values (7-28 ng•mL-1). The present findings suggest oral SR tablet and suppository rectal formulation have similar pharmacokinetic behavior and would not have suitable pharmacokinetic characteristics to be administered once-a-day as an effective and safe treatment for pain in dogs
PHARMACOKINETICS OF TRAMADOL AFTER PRE-ADMINISTRATION OF FREEZE-DRIED GRAPEFRUIT JUICE IN BEAGLE DOGS
No full textDIFFERENCES IN CONCENTRATIONS OF TRAMADOL AND ITS MAJOR METABOLITES AFTER PER OS SUSTAINED RELEASE TABLET OR PER RECTUM SUPPOSITORY APPLICATION
No full textPHARMACOKINETIC OF TRAMADOL AND ITS MAJOR METABOLITES AFTER INTRAVENOUS AND INTRAMUSCULAR INJECTIONS IN ALPACAS (VICUGNA PACOS)
No full textThe objective of this study is to test the intravenous and intramuscular administration of tramadol
in alpacas (Vicugna pacos), to assess both its pharmacokinetic properties and its safety profile. The study
design comprised a 2 groups, single dose, 2 treatments, 2 periods, randomised, open, balanced, cross-over
design. Eight healthy male alpacas (Vicugna pacos), aged 5-9 years, and weighing 41-58 kg were selected.
After both the administrations of tramadol (2.5 mg/kg), the concentration of tramadol and its main
metabolites, M1, M2 and M5, were determined in plasma using an HPLC method. Moderate side-effects
were shown after IV administration. The intramuscular bioavailability of the drug (81.5%) was within the
generally accepted values for a positive bioequivalence decision of 80-125%. After the intramuscular
injection the mean plasma drug concentration peak was reached after a Tmax of 0.16 h with a Cmax of 1.25
μg/mL. The minimal effective plasma concentration was reached after few seconds following intramuscular
dosing and maintained for about 2-3 h in both administrations. The plasma concentrations of M1 and M5
were low and the amounts of the M2 produced were analogous in both routes of administration.
In conclusion, tramadol was rapidly and almost completely absorbed after IM administration and
its systemic availability was equivalent to the IV injection. The differences in the observed onset time and
duration of action were very small and probably therapeutically irrelevant. Hence, IM injection of tramadol is a useful and better alternative to IV injection in alpaca
Synthesis of variously 1,8-naphthyridine derivatives and evaluation of their antimicobacterial activity
No full textA series of 1,8-naphthyridine derivatives variously substituted in the 2, 3, 4 and 7 positions were synthesized for in vitro evaluation of antimycobacterial activity in accordance with an international program with the tuberculosis antimicrobial acquisition and coordinating facility (TAACF). Several compounds 4, 8, 12, 14, 19, 29 and 30, when tested at a concentration of 6.25 μg/ml against Mycobacterium tuberculosis H37Rv, showed an interesting activity with % inhibition in the range 38-96%. The most effective substituent in position 2, 4 or 7 of the 1,8-naphthyridine nucleus seem to be the piperidinyl group
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