ABSTRACT
Administration of perphenazine, tremorine, nicotine and harmine induced Parkinson-like symptoms in rats and mice. The efficacy of quipazine, a serotonin agonist, in antagonizing these drug-induced Parkinsonian symptoms was assessed. Combinations of this drug with other antiparkinsonian agents such as scopolamine, diphenhydramine and amantadine were also studied in the manifestation of Parkinson-like symptoms in the animal models. The results indicate that quipazine, a central serotonergic agent, counteracted some of the drug-induced symptoms of pseudoparkinsonism in laboratory animals. Cholinergic, dopaminergic and histaminergic receptors play an important role in the manifestations of these symptoms.
Subject(s)
Catatonia/chemically induced , Quinolines/pharmacology , Quipazine/pharmacology , Tremor/chemically induced , Animals , Antiparkinson Agents/pharmacology , Drug Combinations , Drug Interactions , Harmine/pharmacology , Humans , Male , Mice , Nicotine/antagonists & inhibitors , Perphenazine/antagonists & inhibitors , Rats , Tremorine/antagonists & inhibitorsSubject(s)
Benzothiepins/pharmacology , Cyproheptadine/pharmacology , Pizotyline/pharmacology , Thiophenes/pharmacology , 5-Hydroxytryptophan/antagonists & inhibitors , Animals , Antidepressive Agents, Tricyclic/pharmacology , Hypothermia/chemically induced , Mice , Perphenazine/antagonists & inhibitors , Reserpine/antagonists & inhibitorsSubject(s)
Ergot Alkaloids/pharmacology , Acetonitriles/pharmacology , Acetonitriles/therapeutic use , Adrenergic alpha-Antagonists , Animals , Ergolines/pharmacology , Ergolines/therapeutic use , Ergot Alkaloids/history , Ergot Alkaloids/therapeutic use , History, Medieval , History, Modern 1601- , Humans , Perphenazine/antagonists & inhibitors , Prolactin/blood , Structure-Activity RelationshipABSTRACT
A sides of 2-(N-substituted amino)alkoxy-1,1-diphenylethanols was synthesized and evaluated for anticholinergic activity. The compounds differ structurally from the glycolate ester-type anticholinergic compounds by the bioisosteric substitution of a methylene group for the ester carbonyl moiety. The ethers which result from this change have increased lipophilicity compared to their ability to inhibit perphenazine-induced catatonia in rats. Structure-activity relationships of the compounds are discussed.
Subject(s)
Glycolates/chemical synthesis , Parasympatholytics/chemical synthesis , Animals , Body Temperature/drug effects , Catatonia/chemically induced , Catatonia/physiopathology , Chemistry, Pharmaceutical , Glycolates/pharmacology , Humans , In Vitro Techniques , Jejunum/drug effects , Male , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Perphenazine/antagonists & inhibitors , Rabbits , Rats , Solubility , Structure-Activity RelationshipSubject(s)
Ergot Alkaloids/pharmacology , Estradiol/pharmacology , Perphenazine/pharmacology , Prolactin/metabolism , Adrenal Glands/anatomy & histology , Animals , Estrogen Antagonists , Female , Organ Size , Perphenazine/antagonists & inhibitors , Pituitary Gland/analysis , Pituitary Gland/metabolism , Prolactin/blood , Rats , Stimulation, Chemical , Time FactorsSubject(s)
Prostaglandins/pharmacology , Analgesia , Animals , Body Temperature/drug effects , Cerebral Ventricles , Escape Reaction , Injections , Motor Activity/drug effects , Nicotine/antagonists & inhibitors , Pentobarbital , Perphenazine/antagonists & inhibitors , Seizures/prevention & control , Sleep/drug effects , Tremorine/antagonists & inhibitorsSubject(s)
Colchicine/pharmacology , Cytochalasin B/pharmacology , Microtubules/drug effects , Pituitary Gland/drug effects , Pituitary Neoplasms/metabolism , Vinca Alkaloids/pharmacology , Animals , Depression, Chemical , Female , Growth Hormone/biosynthesis , Growth Hormone/metabolism , In Vitro Techniques , Male , Neoplasm Transplantation , Neoplasms, Experimental/metabolism , Perphenazine/antagonists & inhibitors , Pituitary Gland/cytology , Pituitary Gland/metabolism , Prolactin/biosynthesis , Prolactin/metabolism , Rats , Tritium , Vinblastine/pharmacology , Vincristine/pharmacologySubject(s)
Antidepressive Agents/pharmacology , Phenanthridines/pharmacology , Aggression/drug effects , Amphetamine/pharmacology , Analgesics/pharmacology , Animals , Behavior, Animal/drug effects , Cats , Drug Synergism , Electroshock , Escape Reaction/drug effects , Humans , Lethal Dose 50 , Methylamines/pharmacology , Mice , Motor Activity/drug effects , Pentylenetetrazole/antagonists & inhibitors , Perphenazine/antagonists & inhibitors , Postural Balance/drug effects , Rabbits , Rats , Reserpine/antagonists & inhibitors , Salivation/drug effects , Seizures/prevention & control , Sleep/drug effects , Social Behavior/drug effects , Stereotyped Behavior/drug effects , Tremorine/antagonists & inhibitors , Tryptamines/antagonists & inhibitors , Ulcer/prevention & controlSubject(s)
Antiparkinson Agents/therapeutic use , Basal Ganglia Diseases/prevention & control , Glycolates/pharmacology , Thiophenes/therapeutic use , Animals , Benztropine/therapeutic use , Haloperidol/antagonists & inhibitors , Haplorhini , Macaca , Male , Perphenazine/antagonists & inhibitors , Phenothiazines/therapeutic use , Trihexyphenidyl/therapeutic useABSTRACT
1. The pA2 anti-acetylcholine activity in vitro for benapryzine was 6.55 compared with 9.02 for benzhexol.2. In vivo, the anti-acetylcholine activity of benapryzine relative to benzhexol was 0.038 as assessed by the mydriatic response of mice after subcutaneous administration. The relative activity assessed by the inhibition of pilocarpine-induced salivation was 0.13 after oral administration and 0.056 following subcutaneous administration of the drugs.3. Benapryzine had the same order of activity as benzhexol in inhibiting oxotremorine-induced tremors in mice.4. Benapryzine had anticonvulsant properties but no analgesic activity, whilst in high doses it antagonized the extrapyramidal symptoms induced by perphenazine in rats.5. In patients benapryzine was effective in reducing the symptoms of Parkinson's disease without overt anti-cholinergic effects or central hallucinogenic actions.6. Benapryzine abolished the excess tremor and reduced the rigidity and akinesia induced by physostigmine in Parkinsonian subjects.
