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At least 19 recordsLinked to original sources
PubMed1982

Effects of the combination of tripelennamine and pentazocine at the behavioral and molecular levels.

The purpose of the present experiments was to determine if the antihistamine tripelennamine potentiates the morphine-like effects of the narcotic-antagonist analgesic pentazocine at the behavioral level or the molecular level or both. At the behavioral level, the effects of pentazocine were determined alone and in combination with tripelennamine in rats trained to discriminate between saline and either morphine or the psychotomimetic narcotic derivative SKF 10,047. The interaction between pentazocine and tripelennamine were also evaluated in the guinea-pig ileum preparation and in the [3H]-naloxone opiate receptor binding assay. Tripelennamine significantly enhanced the morphine-like discriminative stimulus effects of pentazocine and markedly reduced the SKF 10,047-like stimulus effects of pentazocine. Naloxone antagonized the morphine-like effects of pentazocine plus tripelennamine. Pentazocine significantly constricted pupils in the rat, an effect which was additive with the mydriatic effects of tripelennamine. Inhibition of the twitch-height of the electrically stimulated guinea-pig ileum by pentazocine was not affected by tripelennamine. Further, tripelennamine did not modify the Ke for naloxone in antagonizing pentazocine. Inhibition of specific [3H]-naloxone binding by pentazocine was also not affected by tripelennamine. These results are consistent with the hypothesis that the potentiation of the morphine-like effects of pentazocine by tripelennamine which was observed behaviorally was not due to molecular interactions at the morphine receptor. At least a part of this interaction may be attributable to tripelennamine decreasing the psychotomimetic actions of pentazocine.

Animals↗
PubMed1985

Potentiation of pentazocine antinociception by tripelennamine in the rat.

The effect of tripelennamine on pentazocine antinociception in rats was investigated utilizing a low temperature (51.5 degrees C) hot-plate technique. Tripelennamine (10 and 20 mg/kg i.p.) showed some antinociceptive activity, which was not antagonized by naloxone. Pentazocine antinociception was potentiated by simultaneous administration of a large dose (20 mg/kg) but not a small dose (5 mg/kg) of tripelennamine. Potentiation was not observed when tripelennamine was administered 2 hr before the injection of pentazocine and chronic administration of tripelennamine for 14 days did not alter pentazocine antinociceptive activity. After administration of pentazocine and tripelennamine, levels of pentazocine under concentration-time curves in the brain and plasma were slightly and significantly larger, respectively, than the levels obtained by the administration of pentazocine alone. After the administration of tripelennamine and pentazocine, the brain tripelennamine concentration at 1/4 hr was about 2.6 times that after the administration of tripelennamine alone. The results suggest that the effect of tripelennamine on pentazocine antinociception is additive; very little was through a mechanism of inhibition of pentazocine metabolism.

Analgesia↗
PubMed1984

Potentiation of narcotic-induced antinociception by tripelennamine in morphine-tolerant and drug-naive mice.

The ability of tripelennamine and chlorpheniramine to potentiate morphine- and pentazocine-induced antinociception in drug-naive and morphine-tolerant mice was tested utilizing the hot-plate method. Both tripelennamine and chlorpheniramine alone produced dose-dependent increases in hot plate latency which were naloxone reversible. Cross-tolerance developed between tripelennamine and morphine, whereas no cross-tolerance developed between chlorpheniramine and morphine. Neither tripelennamine nor chlorpheniramine significantly potentiated morphine-induced antinociception in drug-naive mice. The effects of tripelennamine and morphine were additive. Tripelennamine but not chlorpheniramine, however, significantly potentiated antinociception produced by low but not high doses of pentazocine in drug-naive mice. Furthermore, in morphine-tolerant mice, tripelennamine, but not chlorpheniramine, potentiated both morphine- and pentazocine-induced antinociception. It is concluded that the abuse of various narcotic-tripelennamine combinations can be attributed, at least in part, to a specific property of tripelennamine to potentiate narcotic effects in the drug-naive and morphine-tolerant state.

Analgesia↗
PubMed1986

The pharmacokinetics of pentazocine and tripelennamine.

The pharmacokinetics of single and combined doses of pentazocine HCl (40 and 80 mg) and tripelennamine HCl (50 and 100 mg) were studied in six healthy drug abusers. After intramuscular administration of 40 or 80 mg pentazocine alone, mean peak plasma concentrations at 15 minutes were 102 and 227 ng/ml, respectively, and mean plasma t1/2 values were 4.6 and 5.3 hours, respectively. After intramuscular administration of 50 or 100 mg tripelennamine, mean plasma concentrations at 30 minutes were 105 and 194 ng/ml, respectively, and mean plasma t1/2 values were 2.9 and 4.4 hours, respectively. After concurrent administration of pentazocine with tripelennamine, plasma pentazocine and tripelennamine concentrations at all time points were not significantly different from those when pentazocine or tripelennamine was administered alone. Coadministration of pentazocine and tripelennamine had no effect on the distribution, elimination, and clearance of either pentazocine or tripelennamine. In conclusion, there did not appear to be a clinically significant metabolic interaction between pentazocine and tripelennamine.

Adult↗
PubMed1986

The clinical pharmacology of pentazocine and tripelennamine (T's and Blues).

The incidence of abuse of pentazocine and tripelennamine (T's and Blues) suggests that the mixture has greater abuse potential than does either agent alone. Pentazocine (40 and 80 mg), tripelennamine (50 and 100 mg), alone and in combination, and placebo were administered in random order to volunteering experienced drug users. Pentazocine alone and tripelennamine alone were identified as opioids and produced euphoria. The large dose of pentazocine produced sedation and dysphoria. Pentazocine and tripelennamine both raised blood pressure; pentazocine constricted pupils, tripelennamine did not. The addition of 50 mg of tripelennamine increased the euphoric effects of pentazocine and attenuated the dysphoric effects seen at higher doses. Adding 100 mg of tripelennamine did not appreciably increase further the euphoric effects and did not alter the dysphoric effects of high doses of pentazocine. The combination significantly increased the systolic and diastolic blood pressure, and the increase was at least additive. In combination, pupillary constriction was slightly antagonized. These studies suggest that the antihistamine tripelennamine has abuse potential, and that in combination with pentazocine, the euphoric effects of the opioid are enhanced and its dysphoric properties attenuated.

Arousal↗
PubMed1989

Opiate dependence alters central reward of nalbuphine or pentazocine plus tripelennamine.

The threshold lowering effects of the coadministration of tripelennamine plus nalbuphine or tripelennamine plus pentazocine on the threshold for rewarding electrical intracranial stimulation, a model of drug-induced euphoria, was determined in rats physically dependent to morphine. Although tripelennamine plus nalbuphine had threshold-lowering effects similar to tripelennamine plus pentazocine in non-opiate-dependent subjects, tripelennamine plus nalbuphine failed to lower the threshold for rewarding stimulation in morphine-dependent animals. To the extent that these data may be applied to human addicts, it suggests that opiate-dependent addicts are unlikely to use the combination of tripelennamine plus nalbuphine but are likely to use tripelennamine plus pentazocine.

Animals↗
PubMed1988

Tripelennamine fails to enhance the morphine-like stimulus effects of pentazocine.

The effects of tripelennamine alone and in combination with morphine or pentazocine were examined in pigeons trained to discriminate between morphine (5.6 mg/kg, IM) and saline under a fixed ratio 30 schedule of food presentation. Tripelennamine (0.3-10.0 mg/kg) produced only saline-appropriate responding and dose-related decreases in response rates. When administered alone, both morphine (0.3-10.0 mg/kg) and pentazocine (1.0-30.0 mg/kg) produced dose-related increases in morphine-appropriate responding and dose-related decreases in response rates. When tripelennamine (0.3, 1.0 mg/kg) was administered in combination with morphine, the morphine dose-effect curve was not altered. Additionally, when tripelennamine (0.3, 1.0, 1.7 mg/kg) was administered in combination with pentazocine, tripelennamine did not alter the extent to which pentazocine produced morphine-appropriate responding. There was some suggestion that tripelennamine attenuated the effects of high doses of pentazocine; however, this effect did not occur in all pigeons. These results suggest that tripelennamine does not enhance the morphine-like discriminative stimulus properties of pentazocine in the pigeon, as it does in the rat.

Animals↗
PubMed1989

Interactions between pentazocine and tripelennamine on autonomic and nociceptive measures in the dog.

Pentazocine and tripelennamine, which have been abused in combination by humans, were evaluated for pharmacologic interactions on autonomic, behavioral, and antinociceptive measures in chronic spinal dogs. Pentazocine (0.31-5 mg/kg, IV) produced miosis, hypothermia and antinociception which was mediated by spinal and supraspinal reflexes; these effects were antagonized by naltrexone. Tripelennamine (0.63-2.5 mg/kg, IV) elicited mydriasis, hyperthermia and antinociception; these effects were not blocked by naltrexone. Tripelennamine produced antinociception only on the supraspinally-mediated skin twitch reflex. Interactions between pentazocine and tripelennamine varied depending on the response measured. Effects of both drugs on pupils were additive. Temperature effects were infra-additive, with the hyperthermic effects of tripelennamine predominating over the pentazocine hypothermia, resulting in a complete physiologic antagonism of pentazocine hypothermia. Antinociception, measured by flexor reflex depression, represented only the effect of pentazocine, whereas skin twitch reflex antinociception reflected either infra-additive or additive properties. The coadministration of nonconvulsive doses of pentazocine and tripelennamine produced seizures indicating a potentiated adverse interaction. In summary, the patterns of the pentazocine-triplennamine interactions were complex and the effects of tripelennamine could not be attributed to opioid activity.

Animals↗
PubMed1983

Pharmacological studies on supersensitization. X. Effect of tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine on the utilization of calcium in acetylcholine-induced contraction of isolated vas deferens of guinea pig.

Effects of tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine (DBED) and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine (DBPD) on the isotonic contractions of isolated vas deferens of guinea pig were examined. Tripelennamine and DBED potentiated the contractile responses to acetylcholine and potassium chloride in Ca2+-free Tyrode solution. DBPD potentiated the contractile responses to lower concentrations of acetylcholine in Ca2+-free Tyrode solution, but did not affect contractions induced by potassium and higher concentrations of acetylcholine in Ca2+-free Tyrode solution. In depolarized vas deferens, tripelennamine and DBED augmented the maximum response to Ca2+, while DBPD did not affect the maximum response to Ca2+ and decrease the sensitivity to Ca2+. The contractile responses to acetylcholine in standard Tyrode solution were attenuated by lanthanum chloride and the residual contractions were not affected by tripelennamine, DBED and DBPD or decreased by DBPD. The contractile responses to potassium chloride were completely abolished by lanthanum chloride. The half-time of decrease in acetylcholine-contraction in Ca2+-free Tyrode solution was significantly different from that of potassium-contraction in Ca2+-free Tyrode solution. The contractile response of the glycerinated muscle piece of vas deferens to calcium chloride was potentiated by DBED, but was not affected by tripelennamine and DBPD. These results suggest that tripelennamine and DBED facilitate nonselectively the transmembrane influx of calcium from extracellular fluid and superficial calcium-binding sites. In addition, DBED increases the sensitivity of contractile element to cytoplasmic free calcium ion. DBPD potentiates the contractile response without affecting the transmembrane mobilization of Ca2+ induced by excitation of cell membrane.

Acetylcholine↗
PubMed1989

Reinforcing and subjective effects of oral tripelennamine in normal human volunteers.

Tripelennamine is a prescription antihistamine with a history of abuse when combined parenterally with opioids. The present study examined the reinforcing and subjective effects of oral tripelennamine in a group of 18 normal, healthy adults. Self-administration behavior was measured with a discrete-trial choice procedure. Subjects first sampled color-coded capsules containing either placebo or tripelennamine (25 or 50mg). On three subsequent occasions, subjects were allowed to choose which color-coded capsule to self-administer. The number of times subjects chose tripelennamine over placebo was used as the primary index of reinforcing efficacy. Subjective effects questionnaires were used to measure mood before and several times after capsule ingestion. The low dose of tripelennamine produced no significant mood changes relative to placebo, and was chosen on 39% of occasions, not significantly different from chance. The high dose produced mild sedative-like effects, and was chosen on 33% of occasions, significantly less than expected by chance, indicating that this dose was aversive. The results demonstrate that oral therapeutic doses of tripelennamine are not reinforcing and do not produce positive mood changes in subjects without a history of drug abuse.

Journal Article↗
PubMed1985

Discriminative stimulus properties of tripelennamine in the pigeon.

Pigeons trained under a two-key drug discrimination procedure eventually learned to discriminate the antihistaminic tripelennamine (5 mg/kg) from saline. When 0.63-7.5 mg/kg doses of tripelennamine were administered in generalization test sessions, the percentage of responses directed to the tripelennamine-appropriate key varied directly with dose. At certain doses, the discriminative stimulus properties of the antihistaminics, diphenhydramine and pyrilamine, clearly generalized to tripelennamine, whereas intermediate generalization was evident with the antihistaminics, chlorpheniramine and promethazine. Chlorpromazine, cimetidine, d-amphetamine, diazepam, morphine, pentazocine, phenobarbital, and sodium valproate failed to produce tripelennamine-like patterns of responding.

Animals↗
PubMed1991

Potentiation of pentazocine conditioned place preference by tripelennamine in rats.

The effects of tripelennamine on place preference conditioning in rats with pentazocine were investigated. Pentazocine at a dose of 2 mg/kg (IP) slightly, but not significantly, induced a place preference. Concurrent dosing of pentazocine (2 mg/kg, IP) and tripelennamine (2.5 mg/kg, SC) significantly and prominently produced a place preference, although administration of tripelennamine (2.5 mg/kg, SC) alone did not. Chronic infusion of a dopamine D1 receptor antagonist, SCH23390 (1.0 mg/kg/day) during conditioning abolished the appetitive effect of pentazocine potentiated by the combination with tripelennamine. In conclusion, it is suggested that the dopaminergic system, especially at the D1 receptor, plays an important role in the potentiation effect of tripelennamine on the pentazocine-induced place preference.

Animals↗
PubMed1983

Tripelennamine effects on body and organ weights, water intake, and several behaviors of rats.

The effects of 14 daily injections of tripelennamine on several dependent measures were determined in groups of rats that received 0.0 (vehicle only), 2.0, 4.0, 8,0, or 16.0 mg/kg of the drug.l Tripelennamine did not affect body weights, organ weights (heart, liver, adrenals, kidneys), or blood glucose levels. Daily water intake was, however, directly and significantly related to tripelennamine dose. The drug failed to influence performance in a grasping response assay, or locomotion as measured in running wheels when rats received footshocks immediately before assessment of locomotion. Tripelennamine did significantly reduce locomotion when rats were not shocked before testing. Nociception, as measured via a hot-plate assay, also was altered by the drug. Here, rats exposed to 16 mg/kg evinced paw-lick latencies far greater than those that received lower doses. These results indicate that tripelennamine produced observable behavioral effects at doses which are not obviously toxic.

Animals↗
PubMed1989

Tripelennamine interactions with the psychotomimetic sigma agonist N-allylnormetazocine.

The pharmacological effects of individual and combined intravenous doses of the antihistamine tripelennamine and the psychotomimetic sigma benzomorphan opioid derivative, N-allylnormetazocine (NANM), on nociceptive reflexes, autonomic parameters and behavior were assessed in the chronic spinal dog. NANM (1.65 mg/kg, IV) produced antinociception, mydriasis, tachycardia, hyperthermia and behavioral signs of canine delirium. Tripelennamine (1.25 mg/kg, IV) produced antinociception, mydriasis and tachycardia without affecting behavior. The combined effects of the two drugs were additive except for heart rate. However, tripelennamine did not antagonize any of the physiological effects or the signs of canine delirium produced by NANM. The findings are inconsistent with the hypothesis that tripelennamine antagonizes the psychotomimetic NANM-like effects of pentazocine to make pentazocine-tripelennamine combinations (T's and Blues) more desirable as a heroin substitute.

Animals↗
PubMed1990

The role of dopamine in the effects of pentazocine and tripelennamine.

CNS dopamine has been suggested as a mediator in the effects of many drugs of abuse. The present study was conducted to assess the potential dopaminergic activity of pentazocine and tripelennamine combinations (T's and Blues). The effects of pentazocine and tripelennamine, administered alone and in combination with several dopaminergic drugs, on milk drinking were assessed in the rat. Both the opioid and antihistamine were tested in combination with apomorphine and haloperidol. Pentazocine was also tested in combination with the D1- and D2-receptor selective antagonists SCH 23390 and raclopride, and with the D2-receptor agonist quinpirole. Tripelennamine was additionally tested in combination with methamphetamine. Haloperidol and quinpirole pretreatment produced leftward shifts in the pentazocine dose-effect curve while raclopride and SCH 23390 shifted the opioid curve to the right. Doses of apomorphine shifted tripelennamine's dose-effect curve to the left, tripelennamine enhanced the effects of methamphetamine, but haloperidol did not alter the antihistamine's effects. These data suggest dopaminergic involvement in the effects of the opioid and antihistamine.

Animals↗
PubMed1982

Determination of pentazocine and tripelennamine in blood of T's and Blue addicts by gas-liquid chromatography with a nitrogen detector.

A procedure for the quantitative determination of pentazocine (T's) and tripelennamine (Blues) in blood obtained from T's and Blues addicts is described. The underivatized drugs were analyzed by gas-liquid chromatography with a nitrogen detector. The retention times relative to mepivicaine (internal standard) on OV-17 at 220 degrees C were: tripelennamine 0.69 and pentazocine 1.77. The linear ranges of blood standards were: tripelennamine, 0.10-1.00 microgram/ml; pentazocine, 0.50-5.0 microgram/ml. For simultaneous analysis, the within-run and between-run CVs of tripelennamine were 5.6% (n = 23) and 13% (n = 12); and for pentazocine 5.2% (n = 23) and 9.9% (n = 12). Mean recoveries over the range of standards were: tripelennamine, 103% +/- 2.5% (n = 12); pentazocine 77.8% +/- 3.6% (n = 12).

Chromatography, Gas↗
PubMed1982

Pharmacological studies on supersensitization. IX. Non-specific supersensitivity of vas deferens of guinea pig induced by tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine.

Effects of tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine (DBED) and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine (DBPD) on the isotonic contractions of isolated vas deferens of guinea pig were examined. These ethylenediamines, except DBPD, induced slight but significant increase in sensitivity of vas deferens to K+. Tripelennamine induced dose-dependent potentiation to epinephrine and norepinephrine, but tripelennamine-induced augmentation of acetylcholine-contractions was weak and dose-independent. DBED potentiated both catecholamines and acetylcholine in a dose-dependent way and in the same degree. The degree of DBPD-induced augmentation of epinephrine- and norepinephrine-induced contractions was dose-independent and much weaker than that of acetylcholine-contractions. Tripelennamine and DBED did not affect the contractile response to tyramine, while DBPD potentiated the contractile response to tyramine. These results suggest the following possibilities: 1) tripelennamine affects both amine uptake mechanism and beyond receptor mechanism of contractile processes and induced supersensitivity of various stimulants. 2) DBED affects mainly beyond receptor mechanism of contractile processes and augments the contractile responses to various stimulants. 3) The mechanism of DBPD-induced supersensitivity remained obscure, but the inhibition of the metabolic degradation of stimulants was proposed as one of the possible mechanism of supersensitization.

Acetylcholine↗
PubMed1983

Pharmacological studies on supersensitization. XI. Inhibitory effect of dibenamine on tripelennamine-N,N-dimethyl-N',N'-dibenzylethylenediamine- and N,N-dibenzyl-N', N'-dimethyl-1, 2-propanediamine-induced supersensitivity of isolated vas deferens of guinea pig.

Effects of dibenamine on tripelennamine-, N,N-dimethyl-N',N'-dibenzylethylenediamine (DBED)- and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine (DBPD)-induced supersensitivity of isolated vas deferens of guinea pig were examined. Dibenamine attenuated the degree of tripelennamine- and DBED-induced increase in sensitivity to acetylcholine and potassium in standard Tyrode solution, but did not affect the degree of DBPD-induced increase in sensitivity to acetylcholine. Dibenamine diminished the degree of tripelennamine-induced increase, but did not affect the degree of DBED-induced increase, in maximum response to Ca2+ of partially depolarized vas deferens. Dibenamine diminished the degree of tripelennamine- and DBED-induced augmentation of potassium-contraction in Ca2+-free Tyrode solution, but did not affect that of acetylcholine-contraction. These results suggest that dibenamine prevent tripelennamine- and DBED-induced increase in Ca2+-influx (including extracellular Ca2+-superficial Ca2+ exchange) induced by acetylcholine and potassium. It is also suggested that DBPD potentiates acetylcholine-contraction by dibenamine-insensitive mechanisms.

Acetylcholine↗