Central analgesic activity of the aqueous and ethanolic extracts of the leaves of Albizia lebbeck: role of the GABAergic and serotonergic pathways.

Albizia lebbeck Benth. is extensively used in Indian traditional medicine for treating several painful and inflammatory disorders. The possible central analgesic activity and the underlying mechanism of action of the aqueous (AE) and ethanolic extracts (EE) of the leaves of A. lebbeck were investigated in Wistar rats using Eddy's hot plate and the tail flick tests. In order to investigate the underlying mechanism of action, rats were pretreated with naloxone, bicuculline or methysergide and then were administered a per os (p.o.) dose of AE or EE. AE and EE caused a significant (p<0.05) elevation in the mean basal reaction time in the hot plate method and an increase in the latency time in the tail flick method. In rats pretreated with bicuculline and methysergide, a significant (p<0.05) reduction in the analgesic activity was observed in comparison to AE and EE. Thus, AE and EE exhibited significant central analgesic activity and act possibly via the GABAergic and serotonergic pathways. The flavonoids and saponins found in the leaves could be responsible for the observed effect.

Involvement of hypothalamic neuropeptide Y in pentazocine induced suppression of food intake in rats.

The potent orexigenic peptide neuropeptide Y (NPY) has been considered as a possible endogenous ligand for a subpopulation of sigma receptors (SigR). However, their mutual interaction with reference to feeding behavior remains poorly understood. In the present study, we explored the possible interaction between sigma1 receptors (Sig1R) agonist, pentazocine, and NPY on food intake in satiated rats. While pentazocine dose-dependently reduced the food intake, NPY significantly increased it at 2, 4 and 6h post injection time points. In combination studies, pretreatment with NPY (0.1 nmol/rat, intra-PVN) normalized the inhibitory effect of pentazocine (60 µg/rat, intra-PVN) on food intake. Similarly, pre-treatment with pentazocine (30 µg/rat, intra-PVN) significantly antagonized the orexigenic effect of NPY (0.5 and 1.0 nmol/rat, intra-PVN). Moreover, pentazocine treatment decreased NPY immunoreactivity in arcuate (ARC), paraventricular (PVN), dorsomedial (DMH) and ventromedial (VMH) nuclei of hypothalamus. However, no change was observed in lateral hypothalamus (LH). Study implicates the reduced NPY immunoreactivity for the anorectic effect observed following pentazocine injections. Therefore, the concomitant activation of the NPYergic system along with the Sig1R agonist treatment may serve a useful purpose in the management of the unwanted side effects related to energy homeostasis.

Antidepressant-like action of the hydromethanolic flower extract of Tagetes erecta L. in mice and its possible mechanism of action.

OBJECTIVE: Tagetes erecta, the marigold, has commercial and ethnomedicinal use; however, reports concerning its efficacy for the treatment of depression are lacking. This study was carried out to elucidate the antidepressant effect of hydromethanolic flower extract of T. erecta. MATERIALS AND METHODS: Hydromethanolic extract of flowers of Tagetes erecta was subjected to preliminary phytochemical screening. The extract (12.5, 25, and 50 mg/kg, i.p.) was evaluated for antidepressant effect using forced swim test in mice. The mechanism of antidepressant action was further examined using different drugs and imipramine was used as standard drug. RESULTS: T. erecta significantly inhibited the immobility period in forced swim test in mice P<0.05). T. erecta (25 mg/kg, i.p.) enhanced the anti-immobility effect of antidepressant drugs like imipramine, fluoxetine, and p-chlorophenylalanine, an inhibitor of serotonin synthesis significantly attenuated its antidepressant effect. The antidepressant effect of T. erecta in the forced swim test was prevented by pretreatment with L-arginine and sildenafil, whereas pretreatment of mice with nitric oxide synthase inhibitors potentiated the action. Pentazocine, a high-affinity sigma receptor agonist, produced synergism with effective dose of T. erecta while progesterone, a sigma receptor antagonist, reversed the antidepressant effect of T. erecta. However, the locomotor activity was not affected at tested doses. CONCLUSIONS: Serotonergic, nitrergic pathway, and sigma receptors are possibly involved in mediating antidepressant action of T. erecta in mouse forced swim test.

Antinociceptive activity of steroid alkaloids isolated from Solanum trilobatum Linn.

Solasodine (1) was isolated for the first time from the roots of Solanum trilobatum Linn., a member of the Solanaceae, and assessed for its presumed antinociceptive activity using several experimental murine models, viz. the writhing, formalin, and hot plate tests. When used at doses of 2, 4, and 8 mg/kg, this steroidal alkaloid caused a significant and dose-dependent decrease in the nociception induced by an intraperitoneal injection of acetic acid (p < 0.001). It also led to a significant reduction of the painful sensation caused by formalin in both phases of the formalin test (p < 0.001). Furthermore, the alkaloid produced a significant increase in the reaction time in the hot plate test (p < 0.001). These results suggest that solasodine elicited antinociceptive activity through both central and peripheral mechanisms.

Analgesic activity of methanol extract of Eupatorium adenophorum Spreng. leaves.

The methanol extract of the leaves of E. adenophorum (100, 200 and 300 mg/kg, po) showed significant analgesic activity, as compared to standard drugs diclofenac sodium and pentazocine, employing acetic acid-induced writhing test, tail immersion test and tail flick test models.

In vivo evidence for the efflux transport of pentazocine from the brain across the blood-brain barrier using the brain efflux index method.

The efflux transport of pentazocine (PTZ) from the brain across the blood-brain barrier (BBB) was investigated using the Brain Efflux Index method. PTZ was eliminated with the apparent elimination half-life of 13.0 min after microinjection into the parietal cortex area 2 region of the rat brain. The apparent efflux clearance of PTZ across the BBB was 137 microl/min/g brain, which was calculated from the elimination rate constant (5.35 x 10(-2) min(-1) and the distribution volume in the brain (2.56 ml/g brain). The efflux transport of PTZ was decreased in the presence of unlabeled PTZ, suggesting that PTZ is eliminated by a carrier-mediated transport system across the BBB. To characterize the efflux transport of PTZ from the brain in vivo, the effects of several compounds on the efflux transport of PTZ were investigated. P-glycoprotein (P-gp) inhibitors (verapamil and quinidine) reduced the PTZ efflux transport. In addition, the efflux transport of PTZ was inhibited by organic cations such as l-carnitine and tetraethylammonium (TEA), whereas organic anions such as p-aminohippuric acid, probenecid and taurocholate did not affect the PTZ efflux transport. The present results suggest that PTZ is transported from the brain across the BBB via l-carnitine/TEA-sensitive carrier-mediated efflux transport system(s) in addition to P-gp.

Anti-inflammatory and analgesic activity of Indian Hypericum perforatum L.

A standardised 50% aqueous ethanolic extract of the Indian variety of Hypericum perforatum (IHp) was examined for its putative anti-inflammatory and analgesic activity at the doses of 100 and 200 mg/kg, po. The experimental paradigms used were carrageenan induced pedal edema and cotton pellet induced granuloma for anti-inflammatory activity, whereas the tail flick, hot plate and acetic acid induced writhing methods were used to asses analgesic activity. Indomethacin (20 mg/kg, ip) was used as the standard anti-inflammatory drug. Pentazocine (10 mg/kg, ip) and aspirin (25 mg/kg, ip), both clinically used analgesics, were used as standard analgesics for comparison. IHp extract showed significant anti-inflammatory and analgesic activity at both dose levels, in all the paradigms used. Additionally, IHp potentiated the anti-inflammatory activity of indomethacin and analgesic activities of pentazocine and aspirin.

Interaction of pentazocine with calcium channel blocking drugs during chemical and thermal pain in mice.

The present study was designed to investigate the antinociceptive interaction of a clinically used opioid, pentazocine which produces its analgesic effect mainly through kappa receptors, with some calcium channel blockers (CCBs, viz. Diltiazem, flunarizine, nimodipine and verapamil--each representing one chemical class) in formalin and tail flick tests in mice. All the CCBs, except verapamil, significantly inhibited the formalin-induced pain response in a dose-dependent manner. However, none of these drugs affected tail flick latency at any of the studied doses. Pentazocine showed a significant antinociceptive response in both pain models, although a high dose was required to increase the tail flick latency. Pretreatment with all CCBs, individually enhanced the analgesic effect of pentazocine in both formalin and tail flick tests. In the latter test of nociception, a per se ineffective dose of pentazocine, showed a significant analgesic response in presence of CCB dose which itself was not effective in the test. Chronic concomitant administration of diltiazem with pentazocine did not prevent the development of tolerance to the opioid compound. However, diltiazem when given in combination with pentazocine to pentazocine-tolerant animals, it effectively reversed the tolerance. Results of the study thus suggest that concomitant treatment with CCBs, irrespective of their chemical nature, not only potentiate the antinociceptive effect of pentazocine in opioid naive animals in both tonic and acute nociceptive tests but also reverse the pentazocine tolerance.

Pregnancy reduces brain sigma receptor function.

1. Sigma (sigma) receptors have recently been cloned, though their endogenous ligand(s) remain unidentified. However, some neuroactive steroids, such as progesterone, have a high affinity for these receptors. Some sigma ligands, such as DTG, (+)-pentazocine and DHEA, act as sigma 'agonists' by potentiating the neuronal response to NMDA. Others, such as haloperidol, NE-100 and progesterone, act as sigma 'antagonists' by reversing the potentiations induced by sigma 'agonists'. 2. We compared the effects of sigma 'agonists' in four series of female rats: in controls, at day 18 of pregnancy, at day 5 post-partum, and in ovariectomized rats following a 3-week treatment with a high dose of progesterone. 3. In pregnant rats and following a 3-week treatment with progesterone, 10 fold higher doses of DTG, (+)-pentazocine and DHEA were required to elicit a selective potentiation of the NMDA response comparable to that obtained in control females. Conversely, at day 5 post-partum and following the 3-week treatment with a progesterone and after a 5-day washout, the potentiation of the NMDA response induced by the sigma 'agonist' DTG was greater than in control females. 4. The present data suggest that endogenous progesterone acts as an 'antagonist' at sigma receptors. The resulting changes in the function of sigma receptors during pregnancy and post-partum may be implicated in emotional phenomena occurring during these periods.

Differential effects of buprenorphine and pentazocine on the regional cerebral metabolic rate for glucose in the conscious rat.

The effects of buprenorphine (BNP, 10-200 micrograms/kg, i.v.) and pentazocine (PTZ, 2.5-10 mg/kg, i.v.) on the regional cerebral metabolic rate for glucose (rCMRglc) were analyzed in nine anatomically discrete areas of the conscious rat brain by the simultaneous use of [14C]2-deoxyglucose, the glucose analogue that can be phosphorylated in the brain, and [3H]3-O-methylglucose, a nonmetabolizable glucose analogue. Originally, this method was developed by Gjedde and Diemer in the rat and in humans. The rCMRglc was significantly decreased by BNP (100 or 200 micrograms/kg) in most of the brain regions investigated, except the cerebellum. In contrast, PTZ (10 mg/kg) significantly increased rCMRglc in the cerebral cortex and medulla. In the cerebral cortex and medulla, the direction of the effect on rCMRglc was opposite for BNP (22% decrease at the dose of 200 micrograms/kg) and PTZ (22% increase at the dose of 10 mg/kg). These findings strongly suggest that the discrepancies between the marked effects of BNP (a partial mu agonist and kappa antagonist) and PTZ (a mu antagonist and kappa agonist) on rCMRglc reflect the selectivity of agonist action at the different types of opioid receptors, mu and kappa receptors, in the rat brain.

[Secondary-reinforcing effects of opiate agonists in the mouse]. / Vtorichno-podkrepliaiushchie éffekty opiatnykh agonistov u myshei.

Comparative examination of secondary-reinforcing properties of opiate agonists morphine, nalorphine, pentazocine and phencyclidine was carried out on mice using procedure of place preference conditioning in an automatic shuttle-box. Morphine, phencyclidine and pentaxocine (but not nalorphine) produced strong dose-dependent secondary-reinforcing effects. Special features of behavioural manifestations of their secondary-reinforcing action were analyzed in aspect of changes in temporal asymmetry and attendant locomotor activity of animals in the shuttle-box. On the basis of the obtained and literature data, it is suggested that mu- and sigma-opiate receptors mediate secondary-reinforcing effects of opiate agonists.

Cortical and thalamic effects of local application of pentazocine to the rat somatosensory cortex.

Cortical and thalamic somatosensory evoked activity was studied following local application of 3% pentazocine to the primary somatosensory SI area (PSA) or to the parietal association area (PAA) of the rat cerebral cortex. At cortical level pentazocine affected the responsiveness of the two cortical areas in a way at least in part opposite. In PSA it essentially depresses the negative wave of the responses, whereas in PAA it increases both the positive and the negative components of the evoked potentials. The changes observed were restricted to the cortical region on which the drug was applied. At thalamic level, administration of pentazocine to the PSA or the PAA did not modify the bioelectrical activity recorded from the center median-parafascicular complex. It is concluded that pentazocine has a direct influence on cortical neurons involved in somatosensory processes. The failure of pentazocine-induced cortical changes to modulate neuronal activity at thalamic level is discussed.

Effect of opiate analgesia and opioid blockade on urethral mucosal sensitivity threshold.

The effect of opiate analgesics (omnopon, pethidine, pentazocine) on the urethral mucosal sensitivity threshold in 37 patients, and of the potent opiate/opioid antagonist naloxone on 10 volunteers is described. Omnopon and pentazocine caused a significant decrease in sensitivity (p less than 0.02) and naloxone caused a significant increase in sensitivity (p less than 0.02). The results confirm a role for the endogenous opioids in modulating urethral sensitivity, and the implications of this are discussed.

Effect of pentazocine and related compounds on the lipid composition of Ehrlich ascites tumor cells.

The effect of pentazocine and its related compounds on the lipid composition of Ehrlich ascites tumor cells was examined. Ehrlich tumor cells were suspended in Hanks balanced salt solution (pH 7.4) supplemented with 2% bovine albumin (2 x 10(6) cells/ml) and incubated at 37 degrees C for 120 min with and without 10(-3) M of pentazocine, morphine or dihydrocodeine. After incubation, the tumor cell lipids were extracted with chloroform-methanol (2:1, v/v), and they were analyzed quantitatively by the dichromate reduction procedure of Amenta. The tumor cells treated with pentazocine contained lower levels of triglycerides and cholesterol esters as compared with the tumor cells incubated alone. The amounts of triglycerides and cholesterol esters in the tumor cells treated with and without pentazocine were about 82 and 23 mg/10(10) cells and 182 and 55 mg/10(10) cells, respectively (P less than 0.01), whereas there was only a slight difference in the contents of these neutral lipids between the tumor cells treated with and without (10(-3) M morphine or dihydrocodeine. In addition, the fatty acid pattern of triglycerides and cholesterol esters from the pentazocine-treated tumor cells differed markedly from that of the corresponding lipids from the tumor cells incubated alone.

Nociceptive and non-nociceptive responses of neurons in the medial subthalamic region and lateral hypothalamic area of cats and their relationship to the effects of morphine and pentazocine.

Single neuronal activity was recorded extracellularly from the Forel's field (FH), subthalamic region immediately rostral to the FH (STRF), rostral end of the medial subthalamic region (RE) and lateral hypothalamic area (LHA) of the anesthetized cats. Many of the FH, RE and LHA neurons were excited by nociceptive stimulation such as pinching the skin with serrated forceps and/or intra-arterial injection of bradykinin. These nociceptive neurons were also excited by non-nociceptive stimulation such as tap of deep tissues, bending hairs with an air-puff and/or joint rotation. On the other hand, inhibition by both nociceptive and non-nociceptive stimuli was seen in and around the rostral end of the FH including STRF. Their receptive fields were large. After intravenous administration of either morphine or pentazocine, most nociceptive neurons became unresponsive to nociceptive stimuli, although they were driven by non-nociceptive stimuli. This suggests that morphine and pentazocine have a specific antinociceptive action on these nociceptive neurons. Intravenous naloxone reversed the antinociceptive action of morphine, but failed to reduce the action of pentazocine. This differentiation has an important functional significance.

Antinociceptive action of morphine and pentazocine on unit activity in the nucleus centralis lateralis, nucleus ventralis lateralis and nearby structures of the cat.

Single neuronal activity has been recorded extracellularly from the nucleus centralis lateralis (CL), ventralis lateralis (VL) and medialis dorsalis (MD) of the cat thalamus. The majority of the CL, VL and MD neurons were excited by nociceptive stimulation such as pinching the skin with serrated forceps and/or intra-arterial injection of bradykinin. The nociceptive neurons were also driven by non-nociceptive stimulation such as tap of deep tissues, bending hairs and an air-puff and/or joint rotation, and their receptive fields were large. After intravenous administration of either morphine or pentazocine, most nociceptive neurons became unresponsive to nociceptive stimuli, although they were driven by non-nociceptive stimuli. This suggests that morphine and pentazocine have a specific antinociceptive action on these nociceptive neurons. Intravenous naloxone reversed the antinociceptive action of morphine, but failed to reduce the action of pentazocine. This differentiation has an important functional significance.

[Clinical Investigations about the behaviour of pulmonary respiration and cardiovascular circulation after the application of Rohypnol for basis-sedation for microsurgical operations in otolaryngology in local anesthesia (author's transl)]. / Klinische Untersuchungen über das Verhalten von Atmung und Kreislauf bei Verwendung von Rohypnol zur Basissedierung für hals-nasen-ohrenärztliche Eingriffe in Lokalanästhesie.

The influence of analog-sedation on pulmonary respiration and cardiovascular circulation caused by the action of pentazocine/flunitrazepam respectively in microsurgical operations under local anesthesia in otolaryngology is investigated in two collectives of patients. The results are presented and the hazards, especially the hypoxemia and its avoidance are discussed.