Immobilization with a single dose of ketamine hydrochloride and a combination of xylazine hydrochloride-ketamine hydrochloride and antagonism by yohimbine hydrochloride in the Japanese monkey (Macaca fuscata)

Forty-nine free-ranging Japanese monkeys (Macaca fuscata) were immobilized with 4.3–15.6 mg/kg (mean±S.D.=10.0±2.5 mg/kg) of ketamine hydrochloride (HCl), and 27 Japanese monkeys kept in enclosures were immobilized with a combination of 0.8–1.4 mg/kg (1.0±0.2 mg/kg) of xylazine HCl and 4.0–7.1 mg/kg (5.0±0.6 mg/kg) of ketamine HCl. In the xylazine HCl-ketamine HCl combination, good myorelaxation was induced. The mean induction times for the single dosage of ketamine HCl and the xylazine HCl-ketamine HCl combination were 2.8±1.5 min and 6.9±4.4 min, respectively. The mean immobilization times with the single dosage of ketamine HCl and the xylazine HCl-ketamine HCl combination were 39.3±16.5 min and 58.8±34.2 min, respectively. A half dose of ketamine HCl in combination with xylazine HCl could also immobilize Japanese monkeys successfully. Administrations of 0.5 mg/kg i.v. and 1.0 mg/kg i.m. of yohimbine HCl as an antagonist to xylazine HCl at 30 min after the induction reduced the immobilization time to 31.4±0.5 min and 49.0±22.1 min, respectively. Yohimbine HCl appears to be an effective antagonist to combination anesthesia by xylazine HCl-ketamine HCl in the Japanese monkey.     

Opioid modulation of ingestive behaviors in the spiny mouse (Acomys cahirinus)

Feeding and drinking behavior were studied in deprived or sated spiny mice (Acomys cahirinus) at various time intervals following peripheral administration of naloxone hydrochloride and butorphanol tartrate. Naloxone attenuated both food and water intake, but not latency to respond, indicating existence of functional opioid-sensitive feeding and drinking systems in this species. Butorphanol tartrate, a mixed opioid agonist/antagonist produced a dose-related enhancement or suppression of feeding, the former naloxone reversible, but had no measureable effect on drinking.     

Comparison of Neurologic Responses to the Use of Medetomidine as a Sole Agent or Preanesthetic in Laboratory Beagles

Different dose regimens of medetomidine (a potent α2-adrenergic agonist), adding up to a combined dose of 80 µg/kg, were administered to laboratory beagles to determine physiologic responses including neurologic. The study was intended to determine EEG responses where sufficient sedative and analgesic effects are reached with medetomidine and in contrast its effects when used with ketamine or halothane. Cardiopulmonary responses were very similar in each dose regimen, showing the characteristic properties of single doses of 80 µg/kg of medetomidine. Effective sedative and analgesic duration seemed to be a function of when the largest dose was administered. Adequate additional sedative and analgesic could be gained from injections at doses of half of the initial one. The potent sedative and analgesic effects of medetomidine confirmed by neurologic evaluation supports its potential use as a premedication to general anesthesia in dogs. In this study, 2 different doses of medetomidine were also tested as premedication to both ketamine HCl and halothane anesthesia. Neorologic responses were determined at the same time cardiopulmonary parameters, anesthetic quality, and dose requirements were recorded. Medetomidine was found to have favorable qualities in conjunction with these anesthetics. Cardiopulmonary parameters remained satisfactory in both groups as preanesthetic medication prior to halothane, but no additional benefits could be seen from doses of 40 µg/kg medetomidine compared to 20 µg/kg, except a significant 30% reduction in halothane requirement. The positive chronotropic and inotropic properties of ketamine restored the medeto-midine-induced bradycardia and produced a short anesthetic period of 15 to 30 min depending on the dose of medetomidine. The quality of anesthesia was better when 40 µg/kg medetomidine was used, but recorvery was quicker with 20 µg/kg medetomidine. Medetomidine significantly reduced cerebral activity as demonstrated by recordings of total amplitude and frequency evaluation of the EEG with compressed spectral analysis. This analytical method was effective in confirming clinical signs of sedation, analgesia, and anesthesia in canine subjects.     

Microencapsulation by Spray Coagulation of Diltiazem HCl in Calcium Alginate-Coated Chitosan

The aim of this work was to develop a procedure for encapsulation of diltiazem HCl by spray coagulation. Factors affecting the formulations such as the effect of NaCl on the solubility of diltiazem in alginate solution, surface tension, pH, viscosity of the coagulation medium, and the effect of drug load on drug release were studied. The drug load was increased substantially from 10 up to 320 mg/mL by adding 1.2% w/v NaCl in 1% w/v alginate solution. More stable microcapsules were obtained at pH 4.6 (acetate buffer) than at a pH 2.8 (lactic acid), and the microencapsulation process was favored by the type of chitosan that produced low turbidity and viscosity in the coagulation medium. A dose of 50 mg/mL of diltiazem HCl, 1.2% w/v NaCl, and chitosan CS allowed higher amount of drug to be encapsulated. The high water solubility of diltiazem HCl leads to fast release from the microcapsules.     

Anesthesia of wild red howler monkeys (Alouatta seniculus) with medetomidine/ketamine and reversal by atipamezole

Wild red howler monkeys (Alouatta seniculus) were translocated during the flooding of the forest at a hydroelectric dam site in French Guiana. For a variety of minor clinical procedures, 96 monkeys were anesthetized with various intramuscular injections of combinations of medetomidine and ketamine. The howler population was composed of healthy animals (42 males and 54 females) of various ages. Medetomidine (150 μg/kg) associated with ketamine (4 mg/kg) gave the best results and was used on 63 animals. The injection rapidly resulted in complete immobilization with good to excellent myorelaxation. The induction stage was quiet, with absence of both corneal and pedal withdrawal reflexes in 57 animals after 2.9 ± 1.4 min. Six animals required an additional injection. Rectal temperature and respiratory and heart rates decreased during anesthesia, whereas relative oxyhemoglobin saturation increased. One death occurred during anesthesia. One abortion and one death also occurred the day following anesthesia but were more probably a result of capture stress. Atipamezole given i.m. at a dose of five times the medetomidine dose 38.4 ± 8.0 min after the anesthetic injection led to standing recovery in 7.1 ± 4.5 min. Spontaneous recovery occurred in 17 animals before the atipamezole injection after an average of 30.6 ± 9.6 min. Total recovery time was shorter in young animals. Medetomidine/ketamine induced good myorelaxation and provided considerably shortened immobilization duration, which are two notable advantages for field studies. We recommend this association for short procedures including minor surgery in red howler monkeys. Am. J. Primatol. 45:399–410, 1998. © 1998 Wiley-Liss, Inc.     

Effects of 5‐HT1 and 5‐HT 2 Receptor Agonists on Electromagnetic Field‐Induced Analgesia in Rats

Much evidence demonstrates the antinociceptive effect of magnetic fields (MFs). However, the analgesic action mechanism of the electromagnetic field (EMF) is not exactly understood. The aim of the present study was to investigate the effects of 5‐HT₁ and 5‐HT₂ receptor agonists (serotonin HCl and 2,5‐dimethoxy‐4‐iodoamphetamine [DOI] hydrochloride) on EMF‐induced analgesia. In total, 66 adult male Wistar albino rats with an average body mass of 225 ± 13 g were used in this study. The animals were subjected to repeated exposures of alternating 50 Hz and 5 mT EMF for 2 h a day for 15 days. Prior to analgesia tests, serotonin HCl (5‐HT₁ agonist) 4 mg/kg, WAY 100635 (5‐HT₁ antagonist) 0.04 mg/kg, DOI hydrochloride (5‐HT₂ receptor agonist) 4 mg/kg, and SB 204741 (5‐HT₂ antagonist) 0.5 mg/kg doses were injected into rats. For statistical analysis of the data, analysis of variance was used and multiple comparisons were determined by Tukey’s test. Administration of serotonin HCl MF (5 mT)‐exposed rats produced a significant increase in percent maximal possible effect (% MPE) as compared with EMF group (P < 0.05). On the contrary, injection of WAY 100635 to MF‐exposed rats produced a significant decrease in analgesic activity (P < 0.05). Similarly, the administration of DOI hydrochloride significantly increased % MPE values as compared with the EMF group while SB 204741 reduced it (P < 0.05). In conclusion, our results suggested that serotonin 5‐HT₁ and 5‐HT₂ receptors play an important role in EMF‐induced analgesia; however, further research studies are necessary to understand the mechanism. Bioelectromagnetics. 2019;40:319–330. © 2019 Bioelectromagnetics Society.     

Behavioral responses of New Zealand fur seals (Arctophoca australis forsteri) to darting and the effectiveness of midazolam and tiletamine‐zolazepam for remote chemical immobilization

We evaluated the behavioral response of 125 free‐ranging New Zealand fur seals (75 females and 50 males) to darting and the effectiveness and safety of midazolam and tiletamine‐zolazepam for remote chemical immobilization. Behavioral reactions to darting were minor and brief. Overall, severe reactions to darting such as long flight responses (7%) and escape to the sea (7%) were uncommon. Midazolam administered by dart failed to produce a satisfactory level of immobilization. Tiletamine‐zolazepam was administered to 120 animals (35 females and 85 males), 104 of which were successfully immobilized and 16 escaped to the water following darting or attempted net capture. At least 10 of the 16 animals are known to have survived. Tiletamine‐zolazepam caused moderate depression of swimming and diving behavior in the animals that escaped to the water. Data from dive loggers confirmed that seals that escaped remained near the sea surface for extended periods. Tiletamine‐zolazepam administered by dart at a mean dosage of 1.87 ± 0.18 mg/kg for females and 1.49 ± 0.23 mg/kg for males provided effective and safe immobilization, reducing capture stress for both animals and personnel. Although there is still a risk of drugged animals escaping to the water and possibly drowning, this risk is much lower than previously reported for other pinnipeds.     

Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets

The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapiddisintegrating tablet (RDT) of the taste-maske drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8∶2 did not show drug release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1∶1 and 7% wt/wt Polyplasdone XL-10 showed faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t₉₀, 60 seconds) in SGF compared with marketed formulation (t₉₀, 240 seconds;P<.01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets in the oral cavity. Published: June 22, 2007     

DISTRIBUTION OF TARTARIC ACID IN THE LEAVES OF CERTAIN ANGIOSPERMS

Stafford , Helen A. (Reed Coll., Portland, Oregon.) Distribution of tartaric acid in the leaves of certain angiosperms. Amer. Jour. Bot. 46(5): 347–352. 1959.—An optically active isomer of tartaric acid has been definitely identified and quantitatively analyzed in the leaves of 9 species of angiosperms, and trace amounts have been tentatively identified in about 22 others out of 49 species examined. In species where identification was positive, the quantity of tartrate varied from 5 to 200 μmoles/g. fresh wt. of leaf tissue; identification was based on paper chromatography and on the metavanadate colorimetric test. The 9 species include Vitis vinifera, V. labruscana, V. californica, Parthenocissus tricuspidata, P. quinquefolio, Pelargonium hortorum, Bauhinia malabarica, Phaseolus vulgaris, and Coleus blumei. Optical rotation data of the isolated acid indicate that the tartrate in Pelargonium and Parthenocissus quinquefolio is the (+) -isomer similar to that reported for Vitis vinifera, but the opposite to that reported for Bauhinia reticulata. The relationship of tartrate to other organic acids is discussed.     

Intra-specific rDNA-ITS restriction site variation and an improved protocol to distinguish species and hybrids in the Daphnia longispina complex

A collaborative research effort was undertaken to evaluate the robustness of a recently developed genetic tool for species identification of members in the morphologically variable Daphnia longispina species complex. This genetic method, based on restriction fragment length polymorphism (RFLP) of the internal transcribed spacer region (ITS) of nuclear ribosomal DNA (rDNA) with restriction enzymes Mwo I and Sau96 I [Billiones et al., 2004. Hydrobiologia 526: 43–53], was applied to many different European populations. Results were compared with two or more independently obtained characters (morphology, allozymes, mitochondrial DNA (mtDNA), or cloned rDNA-ITS sequences). Individuals of most taxa were readily identified, but unexpected ITS-RFLP patterns were found in many individuals indicated by other markers to be D. galeata or one of its hybrids. Among 43 investigated D. galeata populations (902 specimen analysed by ITS-RFLP), deviant RFLP fragment patterns occurred in 26 (i.e., more than half) of the populations. The deviant patterns could be attributed to the loss of one single restriction site in the ITS2 region. This loss made the distinction of D. galeata from other species unreliable, and F1 hybrids could not be identified. Future users should be aware of this shortcoming of the Billions et al. [2004. Hydrobiologia 526: 43–53] protocol. As a solution to this problem, we present an improved genetic identification protocol based on a simple double digestion of the rDNA-ITS region with the restriction enzymes BsrB I and EagI. Sequence analyses of rDNA-ITS clones and preliminary testing indicate that the new protocol is unaffected by the rDNA variation which troubled the Mwo I/Sau96 I protocol. Further, the new protocol identifies all European species of the D. longispina complex, as well as their F1 hybrids. However, a wider screening is required to verify its general utility for all species, since yet unknown variation may occur. Guest editor: Piet Spaak Cladocera: Proceedings of the 7th International Symposium on Cladocera     

即时浸酸显著降低滞育家蚕卵的还原型与氧化型谷胱甘肽比值

即时浸酸在阻止家蚕Bombyx mori卵滞育发动的同时, 显著提高了家蚕卵H₂O₂含量。还原型谷胱甘肽（reduced glutathione, GSH）与氧化型谷胱甘肽（oxidized glutathione, GSSG）的比值是一种氧化胁迫状态的动态指标。为了调查即时浸酸是否造成滞育家蚕卵氧化胁迫, 本研究利用分光光度法分别测定了滞育家蚕卵和5 min即时浸酸滞育家蚕卵中GSH和GSSG含量以及谷胱甘肽转移酶（glutathione-S-transferase, GST）活性。结果表明: 处理后24 h, 即时浸酸处理家蚕卵的总谷胱甘肽（GSH+2GSSG）含量、 GSH含量、 GSSG含量、 GSH/GSSG比值和GST活性分别相当于同期滞育家蚕卵的204%, 78%, 550%, 14%和97%。据此推测, 即时浸酸在阻止滞育发动的同时, 可能通过促进GSH氧化为GSSG, 而显著降低了GSH/GSSG比值, 使家蚕卵处于过氧化状态。     

Standardizing methylation method during phospholipid fatty acid analysis to profile soil microbial communities

Phospholipid fatty acid (PLFA) as biomarkers, is widely used to profile microbial communities in environmental samples. However, PLFA extraction and derivatization protocols are not standardized and have widely varied among published studies. Specifically investigators have used either HCl/MeOH or KOH/MeOH or both for the methylation step of PLFA analysis, without justification or research to support either one. It seems likely that each method could have very different outcomes and conclusions for PLFA based studies. Therefore, the objective of this study was to determine the effect of catalyst type for methylation on detecting PLFAs and implications for interpreting microbial profiling in soil. Fatty acid samples extracted from soils obtained from a wetland, an intermittently flooded site, and an adjacent upland site were subjected to HCl/MeOH or KOH/MeOH catalyzed methylation procedures during PLFA analyses. The methylation method using HCl/MeOH resulted in significantly higher concentrations of most PLFAs than the KOH/MeOH method. Another important outcome was that fatty acids with a methyl group (18:1ω,7c 11Me, TBSA 10Me 18:0, 10Me 18:0, 17:0 10Me and 16:0 10Me being an actinomycetes biomarker) could not be detected by HCl/MeOH catalyzed methylation but were found in appreciable concentrations with KOH/MeOH method. From our results, because the HCl/MeOH method did not detect the fatty acids containing methyl groups that could strongly influence the microbial community profile, we recommend that the KOH/MeOH catalyzed transesterification method should become the standard procedure for PLFA profiling of soil microbial communities.     

Quantification of growth factors in allogenic bone grafts extracted with three different methods

Background Bony allografts are used for defect filling. A reliable sterilization method is the peracetic acid–ethanol sterilization procedure (PES). Several studies showed the antimicrobiological efficacy of this method. Aim of this study was the quantification of growth factors necessary for bone formation in PES sterilized allografts (n = 9). Methods To extract the growth factors from the tissue three different methods were used: (a) use of collagenase 1 for extraction, (b) incubation of the material in a proteinase inhibitor cocktail (Complete), and (c) extraction with guanidine HCl. The supernatants from the different methods were analyzed for the total protein concentration and different growth factors. Results The extraction with guanidine HCl resulted in the highest amount of protein measurable in the supernatants of the samples. For comparison of the individual growth factor values the results were normalized to the protein content. The highest growth factor amount/protein was detectable for BMP-2 using the GndHCL method followed by FGFa, IGF-I, TGF-β1, VEGF, and PDGF. Comparing the three extraction methods, significant differences were measured for the individual growth factor content. Conclusion PES sterilized bony allografts contain several growth factors. Depending on the extraction method, the quantity of the analyzed growth factors varies.     

Technique,Safety, and Efficacy of Intra-Abdominal Transmitters in Nine-Banded Armadillos

ABSTRACT The future management of nine-banded armadillos (Dasypus novemcinctus) requires solid space-use and activity data, which are currently lacking and which radiotelemetry can provide. External radiotransmitters have not been successful applied with this species. To make recommendations for intra-abdominal radiotransmitter placement in nine-banded armadillos, we 1) evaluated 4 different anesthetic protocols for safety, efficiency, and cost-effectiveness; 2) evaluated a surgical technique for the intra-abdominal placement of radiotransmitters that addresses problems described in previous studies; and 3) evaluated the physiologic and behavioral effects of such a technique. We captured and surgically implanted 37 nine-banded armadillos using either butorphanol and isoflurane, ketamine alone, ketamine and xylazine, or a combination of butorphanol, ketamine, and medetomidine for anesthesia. We recovered and necropsied armadillos after the completion of the study. The objective and subjective assessment of butorphanol, ketamine, and medetomidine combination protocol, followed by reversal of the anesthesia with atipamezole, showed that it was the best overall anesthetic protocol for field use, providing both a smooth induction and fast recovery. We evaluated the fate and effects of radiotransmitters on 13 recovered animals at the end of the study and found no adverse effects. We recommend the implantation of radiotransmitters that are allowed to free-float within the abdominal cavity and specifically emphasize the need for strict aseptic technique. Wildlife managers and wildlife veterinarians aiming to implant nine-banded armadillos with radiotransmitters will benefit from using the recommended anesthetic protocol and surgical technique in future studies.     

Butorphanol tartrate induces feeding in rats

Peripheral administration of butorphanol tartrate markedly enhanced feeding from 0800 to 1400 hours when compared with vehicle controls. Butorphanol tartrate feeding was not antagonized by doses of naloxone as high as 10 mg/kg. These data support the concept that the kappa or sigma opiate receptors are involved in feeding behavior.It is well recognized that the endogenous opiates play a role in the central regulation of appetite (1, 2, 3, 4). Numerous studies have shown that The endogenous opioid peptides and morphine can initiate feeding under various conditions (5–12) whereas the opiate antagonist, naloxine can reduce food consumption (13–20). Recently, the endogenous opiod peptide, dynorphin, has been reported to enhance food intake (12–25).Much evidence has been accumulated indicating that a number of opiate receptors are present in the brain, each one having a high affinity for a specific endogenous opioid peptide (26, 27). Both the cyclazocine related compounds (28) and the feeding enhancer, dynorphin (29–32), have been reported to be specific kappa receptor agonists. In the present study, we report on the effect of the morphinan congener, butorphanol tartrate (33), on ingestive behaviour.     

Cardiopulmonary effects of nalbuphine hydrochloride and butorphanol tartrate in sheep

The cardiopulmonary, sedative and analgesic effects of butorphanol tartrate and nalbuphine hydrochloride were evaluated in six adult crossbred Dorset sheep (Ovis aries). The animals were divided randomly into two groups of three. The first group received butorphanol tartrate (0.5mg/Kg s.c.) followed in 3 days by nalbuphine hydrochloride (1 mg/Kg, s.c.). The second group received nalbuphine followed in 3 days by butorphanol. Cardiopulmonary parameters were evaluated at baseline (once the animal had accommodated to restraint); immediately following analgesic administration; and at 15, 30, 60, 90 and 120 minutes after analgesic administration. No significant changes (alpha greater than .05) from baseline were seen in any of the measured cardiopulmonary parameters from either the butorphanol or nalbuphine groups. Butorphanol produced the most dramatic analgesic and sedative effects with onset of both within 15 minutes of administration and peak effects occurring 30 minutes post injection. The degree of analgesia was diminished at 120 minutes while the sedative effect returned to near baseline by 90 minutes. The nalbuphine group also showed an onset of analgesia 15 minutes post injection reaching a peak effect after 30 minutes. However, onset of sedation occurred 30 minutes post injection achieving a peak effect at 60 minutes which was markedly less than that of butorphanol. As in the butorphanol group, analgesia was diminished at 120 minutes.     

A Novel Approach to Optimize and Formulate Fast Disintegrating Tablets for Nausea and Vomiting

The aim of this study was to optimize and formulate fast disintegrating tablets (FDTs) for nausea and vomiting using aminoacetic acid, carmellose and sodium alginate with enough mechanical strength. Ondansetron HCl (water soluble) or domperidone (water insoluble) drug were added to FDTs and their disintegration behaviour was evaluated. Plackett Burman Screening Design was used to screen the independent active process variables [concentration of aminoacetic acid (X ₁), concentration of carmellose (X ₂) and tablet crushing strength (X ₃)] which were found to actively influence the dependent variables [disintegration time in the mouth (DT), wetting time (WT), and water absorption ratio (WAR)] for both the drugs. Also, the coefficients of active variables (DT, WT and WAR) of FDTs containing domperidone was found to be significantly different (P < 0.05) from the coefficients of active factors (X ₁, X ₂ and X ₃) containing ondansetron HCl FDTs. Further, FDTs containing domperidone was prepared according to central composite design for estimating the effect of active factors (X ₁, X ₂, X ₃) in extended spherical domain. The regression analysis of quadratic fit revealed that DT, WT and WAR were 98% correlated with active factors (X ₁, X ₂ or X ₃). The optimized domperidone FDTs were further compared with superdisintegrants (croscarmellose sodium or crospovidone). The data revealed that optimized domperidone FDTs were better than domperidone FDTs containing croscarmellose or crospovidone. Hence, this novel excipients combination can be used for delivery of water insoluble drugs in place of superdisintegrants.     

Field Sedation of Coyotes,Red Foxes,and Raccoons With Medetomidine and Atipamezole

Abstract: We chemically restrained free-ranging coyotes (Canis latrans), red foxes (Vulpes vulpes), and raccoons (Procyon lotor) using medetomidine antagonized by atipamezole. All coyotes and 80% of red foxes were sedated with mean ± standard deviation doses of 0.12 ± 0.02 mg/kg and 0.14 ± 0.02 mg/kg medetomidine, respectively. Seventy-seven percent of raccoons were sedated with 0.21 ± 0.05 mg/kg medetomidine. In all species we observed occasional movement, muscle rigidity, and partial-arousal during sedation. Animals were alert within 4.3–8.6 ± 3.5–8.4 min following atipamezole at 0.4 mg/kg. Medetomidine and atipamezole provided safe handling in most animals and rapid recovery without use of a controlled substance. At these doses, biologists in the field should be prepared to administer a supplementary dose of medetomidine to some animals depending on ambient conditions and the objectives of the restraint event.     

Contrasting Neurochemical Interactions of Tiletamine, a Potent Phencyclidine (PCP) Receptor Ligand, with the N-Methyl-D-Aspartate-Coupled and -Uncoupled PCP Recognition Sites

Neurochemical interactions of tiletamine, a potent phencyclidine (PCP) receptor ligand, with the N-methyl-D-aspartate (NMDA)-coupled and -uncoupled PCP recognition sites were examined. Tiletamine potently displaced the binding of [3H]1-(2-thienyl)cyclohexylpiperidine with an IC50 of 79 nM without affecting sigma-, glycine, glutamate, kainate, quisqualate, or dopamine (DA) receptors. Like other PCP ligands acting via the NMDA-coupled PCP recognition sites, tiletamine decreased basal, harmaline-, and D-serine-mediated increases in cyclic cGMP levels and induced stereotypy and ataxia. Tiletamine was nearly five times more potent than PCP at inhibiting the binding of 3-hydroxy[3H]PCP to its high-affinity NMDA-uncoupled PCP recognition sites. However, following parenteral administration, dizocilpine maleate (MK-801), ketamine, PCP, dexoxadrol, and 1-(2-thienyl)cyclohexylpiperidine HCl, but not tiletamine, increased rat pyriform cortical DA metabolism and/or release, a response modulated by the NMDA-uncoupled PCP recognition sites. Pretreatment with tiletamine did not attenuate the MK-801-induced increases in rat pyriform cortical DA metabolism, a result suggesting that tiletamine is not a partial agonist of the NMDA-uncoupled PCP recognition sites in this region. However, following intracerebroventricular administration (100-500 micrograms/rat), tiletamine increased pyriform cortical DA metabolism with a bell-shaped dose-response curve. These data indicate a differential interaction of tiletamine with the NMDA-coupled and -uncoupled PCP recognition sites. The paradoxical effects of tiletamine suggest that tiletamine might activate receptor(s) or neuronal pathways of unknown pharmacology.