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Biomedical subjects

L M Gunne

Publications and source records attributed to L M Gunne.

At least 55 records · Page 3Linked to original sources
PubMed1982

Bromocriptine in tardive dyskinesia.

Five schizophrenics and one alcoholic with tardive dyskinesia were given bromocriptine for two 8-week periods. The first trial was made during neuroleptic treatment and the second following a 3 weeks' wash-out of neuroleptics. When neuroleptics were given bromocriptine was essentially without effects, but after the neuroleptics had been discontinued the same bromocriptine treatment caused amelioration of dyskinesia in three and aggravation in two subjects. During the second bromocriptine trial all schizophrenic patients showed deterioration of psychotic symptoms followed by a reduction of symptoms when bromocriptine was discontinued.

Aged↗
PubMed1982

A model for oral dyskinesia in rats.

Rats subjected to bifrontal cortical ablations developed vacuous chewing movements and jaw tremors that began 22 weeks after surgery, reached a peak rate of 4 to 8 per minute, and remained stable for an 8-week observation period. Chronic haloperidol administration to rats with bifrontal cortical ablations produced 15 to 20 movements per minute that persisted for 7 weeks after drug withdrawal. Drugs given to decrease dopaminergic, cholinergic, and gamma-aminobutyric acid (GABA)-ergic neurotransmission suppressed the movements, whereas cholinergic agonists increased them. This model of oral dyskinesia in rats may be useful in developing drugs for the treatment of facial dyskinesias in humans.

Animals↗
PubMed1981

The Swedish methadone maintenance program: a controlled study.

Thirty-four drug addicts, aged 20 - 24 years, with a history of 4 - 8 years of intravenous heroin abuse, were randomly assigned either to a methadone maintenance treatment (MMT) (17) or to an untreated group (17). The untreated controls could not apply for entrance to the program until two years later. It was found that after two years 12 MMT patients had abandoned their drug habits and begun work, whereas 5 had recurrent drug abuse problems. Of the controls, one was drug-free and gainfully employed, 12 were continuously abusing heroin (3 of these had incurred potentially fatal diseases in consequence), 2 were in prison and 2 had diet. Two to seven years after their first visit to the Psychiatric Research Center 8 of the original control group have been accepted into the program. At present 19 (out of 25 admitted) are gainfully employed and no longer abusing drugs. Among the remaining controls 4 are dead, 3 are in prison, one in spite of a serious heart condition abuses heroin and one is drug-free. The rehabilitation rate was thus 76 per cent in the program as compared to 6 per cent among the control group. In addition, MMT obviously reduced the high morbidity and mortality rates found in a selection of heroin addicts who fulfilled the admittance criteria of the Swedish program.

Adult↗
PubMed1981

CSF-endorphins in heroin addicts during methadone maintenance and during withdrawal.

Seventeen opiate-dependent subjects accepted for methadone maintenance treatment were housed in a closed metabolic ward. They stayed drug-free for 3 weeks before methadone treatment was started. One sample of cerebrospinal fluid was taken immediately before the first methadone dose and another sample was taken after the patient had received methadone daily for 3 weeks. Fraction I and II endorphin levels were frequently pathological on both occasions, either elevated or reduced when compared with 19 healthy volunteers. Subjects with pathological pre-treatment levels of both fractions seemed to respond better to the methadone treatment that those with at least one pre-treatment value within the normal range.

Adult↗
PubMed1980

A Swedish drug abuse warning network.

During the period June 1971-December 1976 a total of 592 consecutive admissions to a Drug Addiction Clinic were asked which drugs they had been taking since their first contact with the illegal drug market. Nine drugs belonging to the opiate group, five different amphetamines, five hallucinogens, cocaine and cannabis were mentioned and the patients were asked to specify which year or years they had self-administered any of the drugs mentioned. No attempts were made to quantify the individual drug consumption. The amphetamines and cannabis dominated in the mid sixties, but from then on recorded used of these drugs declined. From 1965 there was a constant increase in the reported use of opiates up to a maximum of 55 per cent of the patients in 1976. The opiates seem to have been introduced on to the market in the order of increasing potency. Morphine base replaced raw opium in the early seventies but was later succeeded by heroin. Hallucinogens, except for a short period around 1969 when 11 per cent of our patients mentioned them, never seemed to reach important levels. A small but growing proportion of our patients have mentioned use of cocaine in the seventies.

Amphetamines↗
PubMed1980

Application of a synthetic enkephalin analogue during heroin withdrawal.

The effects of 20 mg morphine HCL i.m. and the synthetic metenkephalin analogue FK 33-824 (1.25 mg, i.m.) were compared single blind in 8 addicts undergoing withdrawal from chronic heroin misuse. FK 33-824 was found to reduce withdrawal distress in 6 subjects but was less effective than distress in 6 subjects but was less effective than morphine. The effect of FK 33-824 was described as not morphine-like "an intoxication without euphoria". All 8 subjects preferred morphine to FK 33-824 and five stated that they would refuse to take another dose of FK 33-824. This difference in preference, with regard to the two drugs of substitution, may have been due to side-effects of the enkephalin-like compound: a feeling of oppression in the chest and heaviness in muscles.

D-Ala(2),MePhe(4),Met(0)-ol-enkephalin↗
PubMed1979

A monitoring test for the liability of neuroleptic drugs to induce tardive dyskinesia.

Two Cebus apella monkeys with haloperidol-induced tardive dyskinesia have been studied. Substitution of chlorpromazine, thioridazine, clozapine, melperone, or fluphenazine for the daily haloperidol administration temporarily reduced the signs of tardive dyskinesia. In a monkey with low-grade symptoms, persisting for more than 100 days after withdrawal of haloperidol, neuroleptic drugs induced a typical sequence of events: first the dyskinetic movements were abolished, but 1--3 days after administration of a single dose of a neuroleptic drug there was a rebound worsening of symptoms. It was noticed that this aggravation of symptoms corresponded in magnitude and duration to the approximate liability of each compound to induce tardive dyskinesia in man. It is therefore suggested that this animal model could be used to monitor neurological side effects in neuroleptic drugs.

Animals↗
PubMed1979

Pharmacokinetics of methadone during maintenance therapy: pulse labeling with deuterated methadone in the steady state.

A technique is presented for study of steady state kinetics of methadone using pulse labeling with deuterated methadone (d3) and mass fragmentography to measure both unlabeled and labeled methadone in blood. Seven subjects maintained on methadone for at least 10 months were admitted to a closed metabolic ward. The daily dose of unlabeled methadone (d0) was substituted by one dose of methoadone-d3 and plasma levels of methadone-d0 and methadone-d3 were followed for 48 h using a precise (SD +/- 5%) and sensitive (30 pmol/ml) mass fragmentographic technique. Plasma half-lives (T1/2) for both methadone-do and methadone-d3 were calculated from samples obtained 8--24 H following the dose of methadone-d3. The t1/2 of oral methadone-d3 was shorter (22 +/- 2 h) than that of methadone-d0 (52 +/- 20 h). The same pattern was observed after intravenous administration. The results indicate multiple pools of methadone in the body.

Administration, Oral↗
PubMed1979

Pharmacological modification of experimental tardive dyskinesia.

Cebus apella monkeys subjected to chronic haloperidol administration develop neurologic disturbances very similar to neuroleptic-induced acute dystonia human beings. After varying lengths of time, certain monkeys develop a prolonged dyskinetic syndrome resembling tardive dyskinesia (TD), as seen clinically. Two monkeys with signs of TD were given single intramuscular injections of various compounds with known effects on the catecholaminergic, cholinergic, serotoninergic and GABA-ergic neurotransmittor systems, and their effect on the TD signs were rated. Dopamine receptor blockers as well as cholinergics had an ameliorating effect on the symptoms. Some compounds known to activate the GABA system, including some benzodiazepines and the GABA-transaminase inhibitor amino-oxyacetic acid, also reduced the symptoms, as did the serotonin precursor L-5HTP. Results with serotonin antagonists were equivocal. It is concluded that dopamine receptor blockade, as well as increased activity within the GABA-ergic or cholinergic systems cause alleviation of TD. The findings are in agreement with earlier reports in man and thus seem to validate this primate model.

Animals↗
PubMed1979

Development of acute dystonia and tardive dyskinesia in cebus monkeys.

In 4 out of 11 cebus apella monkeys given haloperidol (0.05 - 1.0 mg/kg/d) orally for up to 35 months signs of tardive dyskinesia (TD) hav developed: 1) One monkey developed barely noticeable TD after 4 months, but showed marked and increasing symtpoms of both generalized choreic and buccolingual TD after 8 months. This animal died 3 months after discontinuation of haloperidol. At that time the signs of TD were still prominent. 2) In one monkey bucco-lingual TD appeared after 3 months and was still reversible on discontinuation of haloperidol at 5 months. After a further 12 months of haloperidol, the TD signs proved to be long lasting, possibly irreversible, in this animal. 3) A third monkey showed slight and transient signs of TD at 14 months, but following a further 20 months af haloperidol administration a choreiform syndrome became porminent after drug withdrawal. 4) After 34 months a similar syndrome of choreic movements has been noticed in another animal, increasing after withdrawal of haloperidol. The other 7 monkeys have received haloperidol for 3 - 15 months, without developing any signs of TD. Attacks of acute dystonia have been noticed in all animals, sometimes necessitating anticholinergic medication or decreases in the daily haloperidol dose.

Animals↗
PubMed1978

Methadone maintenance: plasma levels and therapeutic outcome.

Twenty-one opiate-dependent subjects were inducted into methadone maintenance treatment (MMT) in a closed metabolic ward. A daily dose of 30 mg of d, 1-methadone was given for 10 to 24 days followed by 60 mg/day for another 10 to 24 days. Analysis of plasma levels at 4-day intervals showed accumulation to a peak followed by a decrease to a lower level, indicative development of dispositional tolerance. The outcome of treatment was assessed after 21 to 43 mo (median, 33 mo). The best record of rehabilitation was obtained in subjects discharged with steady-state plasma concentrations above 200 ng/ml. Lower levels of plasma methadone were associated with higher frequency of urines containing illicit drugs and poorer psychosocial rehabilitation. This study indicates that a pharmacokinetically optimized dosage regimen would be useful in increasing the therapeutic effectiveness of MMT.

Adult↗
PubMed1978

Endorphins in human cerebrospinal fluid: clinical correlations to some psychotic states.

The significance of endorphins, endogenous morphine-like agents, in some psychiatric disorders was investigated. Samples of cerebrospinal fluid were taken by lumbar puncture from healthy volunteers and from patients with schizophrenic, manic-depressive and puerperal psychosis and analyzed for two major fractions of endorphins (Fractions I and II). In 19 healthy volunteers the levels of the two fractions fell within a fairly narrow range. In contrast, six out of nine drug-free and symptom-rich schizophrenics showed elevated levels of Fraction I, which returned to normal or slightly supranormal values after treatment with neuroleptics or propranolol. This decrement was paralleled by a clinical improvement in four of six responding patients. In four manic-depressive patients, serial samples of cerebrospinal fluid revealed elevated endorphin levels, particularly Fraction I during the manic stage. In three out of four patients with puerperal psychosis, the levels of endorphins (either Fraction I or II) were elevated in the acute drug-free stage. During a later symptom-free stage, after treatment with ECT and/or neuroleptics, the endorphin levels were within the normal range. The present data lend credit to the hypothesis that endorphins are involved in some psychotic states in the human.

Adult↗
PubMed1977

[The drug career].

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Antisocial Personality Disorder↗
PubMed1977

Naloxone-induced reversal of schizophrenic hallucinations.

In a single-blind pilot study 0.4 mg naloxone i.v. was found temporarily to reduce or abolish auditory hallucinations in four cases of chronic schizophrenia whereas saline was without effect. In one of these patients there was a similar reversal also of her visual hallucinations. Two additional cases who denied hearing voices before the injections, reported no subjective effects.

Adult↗